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Artificial Life and Therapeutic Vaccines Against Cancers that Originate in Viruses

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Global Virology III: Virology in the 21st Century

Abstract

The construction of artificial life processes that seek to contribute to the development of therapeutic vaccines to treat human cancers, which have their origin in infectious processes caused by viruses, requires research on three fronts. On the one hand, to know the life cycle of the virus under study, as well as to recognize the mechanisms and strategies that it can implement to attack its host and proceed to infect it. On the other hand, to acknowledge the components, mechanisms and strategies that the immune system develops to identify the presence of a stranger and prepare to repel it, in response to the kind of attack that poses. And finally, to design the strategies, that exogenously, allow activating the host’s immune system so that it prepares answers with objectives aimed at counteracting the injuries caused by the virus that attacks it. This chapter describes in general, the methods that through a process of artificial life, allow to simulate the interactions that arise between human immune system, pathogen (viruses as etiological agents of cancer), and therapeutic vaccines to treat lesions that originates in the activity of this type of pathogen.

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References

  1. Globocan. Estimated cancer incidence, mortality and prevalence worldwide in 2012. France. 2012. http://globocan.iarc.fr/Default.aspx. Accessed 24 Mar 2018.

  2. International Agency for Research on Cancer (IARC). Cancers attributable to infections. France. 2018. https://gco.iarc.fr/infections/help. Accessed 24 Mar 2018.

  3. Katz JS. What is a complex innovation system? In SPRU Working paper Series. Ciarli T, Rotolo D, editors. University of Sussex. Montreal, Quebec, Canada. 2015, Jul. ISSN: 2057-6668.

    Google Scholar 

  4. Meyers RA, editor. Encyclopedia of complexity and systems science. SpringerScience+BusinessMedia, LLC., New York; 2009; p. 92–271. ISBN: 978-0-387-30440-3.

    Google Scholar 

  5. Merelli E, Rucco M, Sloot P, Tesei L. Topological characterization of complex systems: using persistent entropy. Entropy. 2015;17(10):6872–92. https://doi.org/10.3390/e17106872.

    Article  Google Scholar 

  6. Sayama H, editor. Introduction to the modeling and analysis of complex systems. Binghamton University, SUNY. 2015. ISBN 978-1-942341-08-6.

    Google Scholar 

  7. Mitleton-Kelly E, editor. Complex systems and evolutionary perspectives on organisations: the applications of complexity theory to organisations. Advances series in management. Oxford, UK: Elsevier Science Ltd; 2003. ISBN 9780080439570.

    Google Scholar 

  8. Mitchell M, Newman M. Complex systems theory and evolution. In: Pagel M, editor. Encyclopedia of evolution. New York: Oxford University Press; 2002. ISBN: 978-0-195-12200-8.

    Google Scholar 

  9. Martínez-García M, Hernández-Lemus E. Health systems as complex systems. Am J Oper Res. 2013;3(1A):113–26. https://doi.org/10.4236/ajor.2013.31A011.

    Article  Google Scholar 

  10. Ellis B, Herbert SI. Complex adaptive systems (CAS): an overview of key elements, characteristics and application to management theory. Inform Prim Care. 2011;19(1):33–7. https://doi.org/10.14236/jhi.v19i1.791.

    Article  PubMed  Google Scholar 

  11. Pathak SD, Day JM, Nair A, Sawaya WJ, Kristal MM. Complexity and adaptivity in supply networks: building supply network theory using a complex adaptive systems perspective. Decis Sci. 2007;38(4):547–80. https://doi.org/10.1111/j.1540-5915.2007.00170.x.

    Article  Google Scholar 

  12. Alcocer-Cuarón C, Rivera AL, Castaño VM. Hierarchical structure of biological systems. A bioengineering approach. Bioengineered. 2014;5(2):73–9. https://doi.org/10.4161/bioe.26570.

    Article  PubMed  Google Scholar 

  13. Qian H. Stochastic physics, complex systems and biology. Quantitative Biol. 2013;1(1):50–3. https://doi.org/10.1007/s40484-013-0002-6.

    Article  Google Scholar 

  14. Voit EO, editor. A first course in systems biology. Chapter 1: biological systems. New York: Garland Science; 2012; 496 p . ISBN: 9789-0815344674.

    Google Scholar 

  15. Gunawardena J. Biological systems theory. Science. 2010;328(5978):581–2. https://doi.org/10.1126/science.1188974.

    Article  CAS  PubMed  Google Scholar 

  16. Harvard Medical School. What is immunology? Boston, MA. 2015. https://immunology.hms.harvard.edu/about-us/what-is-immunology. Accessed 20 Nov 2015.

  17. Affymetrix-eBioscience. Cytokines-Atlas. Headquarters San Diego, CA 92121.USA. 2015. http://www.ebioscience.com/knowledge-center/antigen/cytokines.htm. Accessed 20 Nov 2015.

  18. American Cancer Society (ACS). Cancer prevention and early detection facts and figures 2015–2016. Atlanta: American Cancer Society. p. 2015.

    Google Scholar 

  19. Parkin J, Cohen B. An overview of the immune system. Lancet. 2001;357(9270):1777–89. https://doi.org/10.1016/S0140-6736(00)04904-7.

    Article  CAS  PubMed  Google Scholar 

  20. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449(7164):819–26. https://doi.org/10.1038/nature06246.

    Article  CAS  PubMed  Google Scholar 

  21. Arazi A, Pendergraft WF III, Ribeiro RM, Perelson AS, Hacohen N. Human systems immunology: hypothesis-based modeling and unbiased data-driven approaches. Semin Immunol. 2013;25(3):193–200. https://doi.org/10.1016/j.smim.2012.11.003.

    Article  CAS  PubMed  Google Scholar 

  22. Stern PL, Einstein MH. Chapter 3 the immunobiology of human papillomavirus associated oncogenesis. In: Borruto F, De Ridder M, editors. HPV and cervical cancer: Springer Sicence+Business Media, LLC; 2012a. p. 45–61. https://doi.org/10.1007/978-1-4614-1988-4_3.

    Chapter  Google Scholar 

  23. Stern PL, van der Burg SH, Hampson IN, Broker TR, Fiander A, Lacey CJ, et al. Therapy of human papillomavirus-related disease. Vaccine. 2012;30S(5):F71–82. https://doi.org/10.1016/j.vaccine.2012.05.091.

    Article  CAS  Google Scholar 

  24. Timmis J, Knight T, de Castro LN, Hart E. An overview of artificial immune systems. In: Paton R, Bolouri H, Holcombe M, Tateson R, editors. Computation in cells and tissues, Natural Computing Series. Berlin, Heidelberg: Springer; 2004. ISBN: 978-3-642-05569-0.

    Google Scholar 

  25. Chu LH, Gangopadhyay A, Dorfleutner A, Stehlik C. An updated view on the structure and function of PYRIN domains. Apoptosis. 2015;20(2):157–73. https://doi.org/10.1007/s10495-014-1065-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Illumina Technology. Immunology research review. An overview of recent immunology research. Publications Featuring Illumina®Technology. 2014. https://www.illumina.com/science/publication-reviews.html. Accessed 30 Dec 2014.

  27. Bourke CD, Prendergast CT, Sanin DE, Oulton TE, Hall RJ, Mountford AP. Epidermal keratinocytes initiate wound healing and pro-inflammatory immune responses following percutaneous schistosome infection. Int J Parasitol. 2015;45(4):215–24. https://doi.org/10.1016/j.ijpara.2014.11.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bernard FX, Morel F, Camus M, Pedretti N, Barrault C, Garnier J, et al. Keratinocytes under fire of proinflammatory cytokines: bona fide innate immune cells involved in the physiopathology of chronic atopic dermatitis and psoriasis. J Allergy. 2012;718725:1–10. https://doi.org/10.1155/2012/718725.

    Article  CAS  Google Scholar 

  29. Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M. Keratins and the keratinocyte activation cycle. J Invest Dermatol. 2001;116(5):633–40. https://doi.org/10.1046/j.0022-202x.2001.doc.x.

    Article  CAS  PubMed  Google Scholar 

  30. Hoffmann GW. Immune network theory. 2nd ed. Burnaby, Canada: Printed by Still Creek Press; 2011. ISBN 978-0-9812196-0-8.

    Google Scholar 

  31. Markham JF, Wellard CJ, Hawkins ED, Duffy KR, Hodking PD. A minimum of two distinct heritable factors are required to explain correlation structures in proliferating lymphocytes. J R Soc Interface. 2010;7(48):1049–59. https://doi.org/10.1098/rsif.2009.0488.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tarlinton D. B-cell differentiation: instructive one day, stochastic the next. Curr Biol. 2012;22(7):R235–7. https://doi.org/10.1016/j.cub.2012.02.045.

    Article  CAS  PubMed  Google Scholar 

  33. Kondo M. Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. Immunol Rev. 2010;238(1):37–46. https://doi.org/10.1111/j.1600-065X.2010.00963.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tobón GJ, Izquierdo JH, Cañas CA. B lymphocytes: development, tolerance, and their role in autoimmunity-focus on systemic lupus erythematosus. Autoimmune Dis. 2013;2013(827254):1–17. https://doi.org/10.1155/2013/827254.

    Article  CAS  Google Scholar 

  35. Ginhoux F, Jung S. Monocytes and macrophages developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014;14(6):392–404. https://doi.org/10.1038/nri3671.

    Article  CAS  PubMed  Google Scholar 

  36. Álvarez-Errico D, Vento-Torm R, Sieweke M, Ballestar E. Epigenetic control of myeloid cell differentiation, identity and function. Nat Rev Immunol. 2015;15(1):7–17. https://doi.org/10.1038/nri3777.

    Article  CAS  PubMed  Google Scholar 

  37. Geissmann F, Manz MG, Jung S, Sieweke M, Merad M, Ley K. Development of monocytes, macrophages and dendritic cells. Science. 2010;327(5966):656–61. https://doi.org/10.1126/science.1178331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bortnick A, Allman D. What is what should always have been: long-lived plasma cells induced T-cell independent antigens. J Immunol. 2013;190(12):5913–8. https://doi.org/10.4049/jimmunol.1300161.

    Article  CAS  PubMed  Google Scholar 

  39. Kalia V, Sarkar S, Gourley TS, Rouse BT, Ahmed R. Differentiation of memory B and T cells. Curr Opin Immunol. 2006;18(3):255–64. https://doi.org/10.1016/j.coi.2006.03.020.

    Article  CAS  PubMed  Google Scholar 

  40. Nutt SL, Hodking PD, Tarlinton DM, Corcoran LM. The generation of antibody-secreting plasma cells. Nat Rev Immunol. 2015;15(3):160–71. https://doi.org/10.1038/nri3795.

    Article  CAS  PubMed  Google Scholar 

  41. Wells A, Gudmundsdottir H, Turka LA. Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response. J Clin Investig. 1997;100(12):3173–83. https://doi.org/10.1172/JCI119873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gudmundsdottir H, Wells AD, Turka LA. Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferativa capacity. J Immunol. 1999;162(9):5212–23.

    CAS  PubMed  Google Scholar 

  43. Sebzda E, Mariathasan S, Ohteki T, Jones R, Bachmann MF, Ohashi PS. Selection of the T cell repertoire. Annu Rev Immunol. 1999;17:829–74. https://doi.org/10.1146/annurev.immunol.17.1.829.

    Article  CAS  PubMed  Google Scholar 

  44. Efroni S, Harel D, Cohen IR. Emergent dynamics of thymocyte development and lineage determination. PLoS Comput Biol. 2007;3(1):e13. https://doi.org/10.1371/journal.pcbi.0030013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fiúza UM, Arias AM. Cell and molecular biology of Notch. J Endocrinol. 2007;194(3):459–74. https://doi.org/10.1677/JOE-07-0242.

    Article  CAS  PubMed  Google Scholar 

  46. Zabriskie J, editor. Essential clinical immunology. New York: The Rockefeller University, Cambridge University Press; 2009. ISBN-13 978-0-521-51681-5.

    Google Scholar 

  47. Henderson A, Calame K. Transcriptional regulation during B cell development. Annu Rev Immunol. 1998;16:163–200. https://doi.org/10.1146/annurev.immunol.16.1.163.

    Article  CAS  PubMed  Google Scholar 

  48. De Wit J, Jorritsma T, Makuch M, Remmerswall EBM, Bos HK, Souwer Y, et al. Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures. J Allergy Clin Immunol. 2015;135(4):1053–60. https://doi.org/10.1016/j.jaci.2014.08.012.

    Article  CAS  PubMed  Google Scholar 

  49. Bachmann MF, Zinkernagel RM. Neutralizing antiviral B cell responses. Annu Rev Immunol. 1997;15:235–70. https://doi.org/10.1146/annurev.immunol.15.1.235.

    Article  CAS  PubMed  Google Scholar 

  50. Mempel TR, Henrickson SE, von-Andrian UH. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature. 2004;427(2970):154–9. https://doi.org/10.1038/nature02238.

    Article  CAS  PubMed  Google Scholar 

  51. Zhu J, Mohan C. Toll-Like receptor signaling pathways-therapeutic opportunities. Mediat Inflamm. 2010;2010(781235):1–7. https://doi.org/10.1155/2010/781235.

    Article  CAS  Google Scholar 

  52. DeCarlo CA, Rosa B, Jackson R, Niccoli S, Escott NG, Zehbe I. Toll-like receptor transcriptome in the HPV-positive cervical cancer microenvironment. Clin Dev Immunol. 2012;2012(785825):1–9. https://doi.org/10.1155/2012/785825.

    Article  CAS  Google Scholar 

  53. Kanneganti T-D. Central roles of NLRs and inflammasomes in viral infection. Nat Rev Immunol. 2010;10(10):688–98. https://doi.org/10.1038/nri2851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. So EY, Ouchi T. The application of Toll like receptors for cancer therapy. Int J Biol Sci. 2010;6(7):675–81. https://doi.org/10.7150/ijbs.6.675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Frazao JB, Errante PR, Condino-Neto A. Toll-like receptors’ pathway disturbances are associated with increased susceptibility to infections in humans. Arch Immunol Ther Exp. 2013;61(6):427–43. https://doi.org/10.1007/s00005-013-0243-0.

    Article  CAS  Google Scholar 

  56. Zhou Q, Zhu K, Cheng H. Toll-like receptors in human papillomavirus infection. Arch Immunol Ther Exp. 2013;61(3):203–15. https://doi.org/10.1007/s00005-013-0220-7.

    Article  CAS  Google Scholar 

  57. Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol. 2012;86(6):2900–10. https://doi.org/10.1128/JVI.05738-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by toll-like receptor 5. Nature. 2001;410(6832):1099–103. https://doi.org/10.1038/35074106.

    Article  CAS  PubMed  Google Scholar 

  59. Basith S, Manavalan B, Yoo TH, Kim SG, Choi S. Roles of Toll-like receptors in cancer: a double-edged sword for defense and offense. Arch Pharm Res. 2012;35(8):1297–316. https://doi.org/10.1007/s12272-012-0802-7.

    Article  CAS  PubMed  Google Scholar 

  60. Ellerman JE, Brown CK, de Vera M, Zeh HJ, Billiar T, Rubartelli A, et al. Masquerader: high mobility group Box-1 and cancer. Clin Cancer Res. 2007;13(10):2836–48. https://doi.org/10.1158/1078-0432.CCR-06-1953.

    Article  CAS  PubMed  Google Scholar 

  61. Goutagny N, Estornes Y, Hasan U, Lebecque S, Caux C. Targeting pattern recognition receptors in cancer immunotherapy. Target Oncol. 2012;7(1):29–54. https://doi.org/10.1007/s11523-012-0213-1.

    Article  PubMed  Google Scholar 

  62. Kim YK, Shin J-S, Nahm MH. Nod-like receptors in infection, immunity, and diseases. Yonsei Med J. 2016;57(1):5–14. https://doi.org/10.3349/ymj.2016.57.1.5.

    Article  CAS  PubMed  Google Scholar 

  63. Eisenbarth SC, Williams A, Colegio OR, Meng H, Strowig T, Rongvaux A, et al. NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells. Nature. 2012;484:510–3. https://doi.org/10.1038/nature11012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Motta V, Soares F, Sun T, Philpott DJ. Nod-like receptors: versatile cytosolic sentinels. Physiol Rev. 2015;95(1):149–78. https://doi.org/10.1152/physrev.00009.2014.

    Article  PubMed  Google Scholar 

  65. Man SM, Kanneganti T-D. Regulation of inflammasome activation. Immunol Rev. 2015;265(1):6–21. https://doi.org/10.1111/imr.12296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sun Q, Fan J, Billiar TR, Scott MJ. Inflammasome and autophagy regulation: a two-way street. Mol Med. 2017;23:188–95. https://doi.org/10.2119/molmed.2017.00077.

    Article  CAS  PubMed  Google Scholar 

  67. Anand PK, Malireddi RKS, Lukens JR, Vogel P, Bertin J, Lamkanfi M, et al. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature. 2012 Aug;488:389–93. https://doi.org/10.1038/nature11250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yan A, Farmer E, Wu TC, Hung CF. Perspectives for therapeutic HPV vaccine development. J Biomed Sci. 2016;23(1):75. https://doi.org/10.1186/s12929-016-0293-9.

    Article  CAS  Google Scholar 

  69. Morrone SR, Matyszewski M, Yu X, Delannoy M, Egelman EH, Son J. Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC. Nat Commun. 2015;6(7827):1–13. https://doi.org/10.1038/ncomms8827.

    Article  CAS  Google Scholar 

  70. Khare S, Ratsimandresy RA, de Almeida L, Cuda CM, Rellick SL, Misharin AB, et al. The pyrin domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nat Immunol. 2014;15(4):343–53. https://doi.org/10.1038/ni.2829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Reinholz M, Kawakami Y, Salzer S, Kreuter A, Dombrowski Y, Koglin S, et al. HPV16 activates the AIM2 inflammasome in keratinocytes. Arch Dermatol Res. 2013;305(8):723–32. https://doi.org/10.1007/s00403-013-1375-0.

    Article  CAS  PubMed  Google Scholar 

  72. Uniprot.org. UniProt: a hub for protein information. Nucleic Acids Res. 43: D204-D212. 2015. http://www.uniprot.org/uniprot/?query=tlr+&sort=score. Accessed 5 Jan 2015.

  73. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511. https://doi.org/10.1038/nri1391.

    Article  CAS  PubMed  Google Scholar 

  74. O’Neill LAJ, Golenbock D, Bowie AG. The history of Toll-like receptors–redefining innate immunity. Nat Rev Immunol. 2013;13(6):453–60. https://doi.org/10.1038/nri3446.

    Article  CAS  PubMed  Google Scholar 

  75. Lim KH, Staudt LM. Toll-like receptor signaling. Cold Spring Harb Perspect Biol. 2013;5(1):a011247. https://doi.org/10.1101/cshperspect.a011247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Amador-Molina A, Hernández-Valencia JF, Lamoyi E, Contreras-Paredes A, Lizano M. Rol of innate immunity against human papillomavirus (HPV) infections and effect of adjuvants in promoting specific immune response. Viruses. 2013;5(11):2624–42. https://doi.org/10.3390/v5112624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Daud II, Scott ME, Ma Y, Shiboski S, Farhat S, Moscicki AB. Association between toll-like receptor expression and human papillomavirus type 16 persistence. Int J Cancer. 2011;128(4):879–86. https://doi.org/10.1002/ijc.25400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hasimu A, Ge L, Li QZ, Zhang RP, Guo X. Expressions of toll-like receptors 3, 4, 7, and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women. Chin J Cancer. 2011;30(5):344–50. https://doi.org/10.5732/cjc.010.10456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Thompson MR, Kaminski JJ, Kirt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011 Jun;3(6):920–40. https://doi.org/10.3390/v3060920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kanzler H, Barrat FJ, Hessel M, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonist and antagonist. Nat Med. 2007;13(5):552–9. https://doi.org/10.1038/nm1589.

    Article  CAS  PubMed  Google Scholar 

  81. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84. https://doi.org/10.1038/ni.1863.

    Article  CAS  PubMed  Google Scholar 

  82. Bonjardim CA. Interferons (IFNs) are key cytokines in both innate and adaptive antiviral immune responses- and viruses counteract IFN action. Microbes Infect. 2005;7(3):569–78. https://doi.org/10.1016/j.micinf.2005.02.001.

    Article  CAS  PubMed  Google Scholar 

  83. Hennessy E, Parker AE, O’Neill LAJ. Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov. 2010;9(4):293–307. https://doi.org/10.1038/nrd3203.

    Article  CAS  PubMed  Google Scholar 

  84. Yarovinsky F. Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol. 2014;14(2):109–21. https://doi.org/10.1038/nri3598.

    Article  CAS  PubMed  Google Scholar 

  85. Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009;9(8):535–42. https://doi.org/10.1038/nri2587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Morrison DK. MAP kinase pathways. Cold Spring Harb Perspect Biol. 2012;4:a011254. https://doi.org/10.1101/cshperspect.a011254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Häcker H, Tseng PH, Karin M. Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol. 2011;11(7):457–68. https://doi.org/10.1038/nri2998.

    Article  CAS  PubMed  Google Scholar 

  88. Hirsch I, Caux C, Hasan U, Bendriss-Vermare N, Olive D. Impaired Toll-like receptor 7 and 9 signaling: from chronic viral infections to cancer. Trends Immunol. 2010;31(10):391–7. https://doi.org/10.1016/j.it.2010.07.004.

    Article  CAS  PubMed  Google Scholar 

  89. Lam LT, Wright G, Davis E, Lenz G, Farinha P, Dang L, et al. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-kB pathways in subtypes of diffuse large B-cell lymphoma. Blood. 2008;111(7):3701–13. https://doi.org/10.1182/blood-2007-09-111948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ngo V, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470(7332):115–21. https://doi.org/10.1038/nature09671.

    Article  CAS  PubMed  Google Scholar 

  91. American Cancer Society (ACS). Cancer immunotherapy. 2018. https://www.cancer.gov/. Accessed 28 May 2018.

  92. Goazigo AR, Steenwinckel JV, Rostène W. Current status of chemokines in the adult CNS. Prog Neurobiol. 2013;104:67–92. https://doi.org/10.1016/j.pneurobio.2013.02.001.

    Article  CAS  Google Scholar 

  93. Hinck AP. Structural studies of the TGF-βs and their receptors – insights into evolution of the TGF-β superfamily. FEBS Lett. 2012;586(14):1860–70. https://doi.org/10.1016/j.febslet.2012.05.028.

    Article  CAS  PubMed  Google Scholar 

  94. Lata S, Raghava GP. Prediction and classification of chemokines and their receptors. Protein Eng Des Sel. 2009;22(7):441–4. https://doi.org/10.1093/protein/gzp016.

    Article  CAS  PubMed  Google Scholar 

  95. Turner MD, Medjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cells signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563–82. https://doi.org/10.1016/j.bbamcr.2014.05.014.

    Article  CAS  PubMed  Google Scholar 

  96. Shaikh PZ. Cytokines & their physiologic and pharmacologic functions in inflammation: a review. Int J Pharm Life Sci. 2011;2(11):1247–63.

    Google Scholar 

  97. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, et al. Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011;127(3):701–721.e1-70. https://doi.org/10.1016/j.jaci.2010.11.050.

    Article  CAS  PubMed  Google Scholar 

  98. Rosa MI, Morales MV, Vuolo F, Petronilho F, Bozzetti MC, Medeiors LR, et al. Association of interleukin-6 in women with persistence of DNA-HPV: a nested case-control study. Arch Gynecol Obstet. 2012;285(1):143–8. https://doi.org/10.1007/s00404-011-1925-7.

    Article  CAS  PubMed  Google Scholar 

  99. Fernandes APM, Goncalves MAG, Duarte G, Cunha FQ, Simoes RT, Donadi EA. HPV16, HPV18, and HIV infection may be influence cervical cytokine intralesional levels. Virology. 2005;334(2):294–8. https://doi.org/10.1016/j.virol.2005.01.029.

    Article  CAS  PubMed  Google Scholar 

  100. Bohnhorst J, Rasmussen T, Moen SH, Flottum M, Knudsen L, Borset M, et al. Toll-like receptors mediate proliferation and survival of multiple myeloma cells. Leukemia. 2006;20(6):1138–44. https://doi.org/10.1038/sj.leu.2404225.

    Article  CAS  PubMed  Google Scholar 

  101. Jego G, Bataille R, Geffroy-Luseau A, Descamps G, Pellat-Deceunynck C. Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Leukemia. 2006;20(6):1130–7. https://doi.org/10.1038/sj.leu.2404226.

    Article  CAS  PubMed  Google Scholar 

  102. Lippitz B. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14(6):e218–28. https://doi.org/10.1016/S1470-2045(12)70582-X.

    Article  CAS  PubMed  Google Scholar 

  103. Padhan K, Varma R. Immunological synapse: a multi-protein signalling cellular apparatus for controlling gene expression. Immunology. 2010;129(3):322–8. https://doi.org/10.1111/j.1365-2567.2009.03241.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Li X, Jiang S, Tapping RI. Toll-like receptor in cell proliferation and survival. Cytokine. 2010;49(1):1–9. https://doi.org/10.1016/j.cyto.2009.08.010.

    Article  CAS  PubMed  Google Scholar 

  105. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472–84. https://doi.org/10.1038/nri1632.

    Article  CAS  PubMed  Google Scholar 

  106. Hu F, Meng Y, Gou L, Zhang X. Analysis of promoters and CREB/AP-1 binding sites of the human TMEM174 gene. Exp Ther Med. 2013;6(5):1290–4. https://doi.org/10.3892/etm.2013.1275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wen AY, Sakamoto KM, Miller LS. The role of the transcription factor CREB in immune function. J Immunol. 2010;185(11):6413–9. https://doi.org/10.4049/jimmunol.1001829.

    Article  CAS  PubMed  Google Scholar 

  108. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-kB signalling pathways. Nat Immunol. 2011;12(8):695–708. https://doi.org/10.1038/ni.2065.

    Article  CAS  PubMed  Google Scholar 

  109. Hoesel B, Schmid JA. The complexity of NF-kB signaling in inflammation and cancer. Mol Cancer. 2013;12:86. https://doi.org/10.1186/1476-4598-12-86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S. Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell. 2003;115(5):565–76. https://doi.org/10.1016/S0092-8674(03)00895-X.

    Article  CAS  PubMed  Google Scholar 

  111. Yuan H, Fu F, Zhuo J, Wang W, Nishitani J, An DS, et al. Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis. Oncogene. 2005;24:5069–78. https://doi.org/10.1038/sj.onc.1208691.

    Article  CAS  PubMed  Google Scholar 

  112. Snow WM, Stoesz BM, Kelly DM, Albensi BC. Roles for NF-kB and gene targets of NF-kB in synaptic plasticity, memory, and navigation. Mol Neurobiol. 2014;49(2):757–70. https://doi.org/10.1007/s12035-013-8555-y.

    Article  CAS  PubMed  Google Scholar 

  113. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114(2):181–90. https://doi.org/10.1016/S0092-8674(03)00521-X.

    Article  CAS  PubMed  Google Scholar 

  114. Sen R. The origins of NF-kB. Nat Immunol. 2011;12:686–8. https://doi.org/10.1038/ni.2071.

    Article  CAS  PubMed  Google Scholar 

  115. Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 2006;25(51):6817–30. https://doi.org/10.1038/sj.onc.1209942.

    Article  CAS  PubMed  Google Scholar 

  116. Spitkovsky D, Hehner SP, Hofmann TG, Möller A, Schmitz ML. The human papillomavirus oncoprotein E7 attenuates NF-kB activation by targeting the IkB kinase complex. J Biol Chem. 2002;277(28):25576–82. https://doi.org/10.1074/jbc.M201884200.

    Article  CAS  PubMed  Google Scholar 

  117. Pradeu T, Kostyrka G, Dupré J. Understanding viruses: philosophical investigation. Studies History Philo Biolog Biomed Sci. 2016;59:57–63. https://doi.org/10.1016/j.shpsc.2016.02.008.

    Article  Google Scholar 

  118. Gibbs AJ, Gibbs MJ. A broader definition of ‘the virus species’ brief report. Arch Virol. 2006;151(7):1419–22. https://doi.org/10.1007/s00705-006-0775-2.

    Article  CAS  PubMed  Google Scholar 

  119. International Committee on Taxonomy of Viruses (ICTV). ICTV Taxonomy. 2018. https://talk.ictvonline.org/taxonomy/w/ictv-taxonomy. Accessed 29 Mar 2018.

  120. Morgan GJ. What is a virus species? Radical pluralism in viral taxonomy. Stud Hist Phil Biol Biomed Sci. 2016;59:64–70. https://doi.org/10.1016/j.shpsc.2016.02.009.

    Article  Google Scholar 

  121. Calisher CH. The taxonomy of viruses should include viruses. Arch Virol. 2016;161(5):1419–22. https://doi.org/10.1007/s00705-016-2779-x.

    Article  CAS  PubMed  Google Scholar 

  122. McLaughlin-Drubin ME, Munger K. Viruses associated with human cancer. Biochim Biophys Acta. 2008;1782(3):127–50. https://doi.org/10.1016/j.bbadis.2007.12.005.

    Article  CAS  PubMed  Google Scholar 

  123. Ahuja R, Jamal A, Nosrati N, Pandley V, Rajput P, Saxena N, et al. Human oncogenic viruses and cancer. Curr Sci. 2014;107(5):768–85.

    CAS  Google Scholar 

  124. Santiago DN, Heidbuechel JPW, Kandell WM, Walker R, Djeu J, Engeland CE, et al. Fighting cancer with mathematics and viruses. Viruses. 2017;9(9):239. https://doi.org/10.3390/v9090239.

    Article  CAS  PubMed Central  Google Scholar 

  125. Flippot R, Malouf GG, Su X, Khayat D, Spano J-P. Oncogenic viruses: lessons learned using next-generation sequencing technologies. Eur J Cancer. 2016;61:61–8. https://doi.org/10.1016/j.ejca.2016.03.086.

    Article  CAS  PubMed  Google Scholar 

  126. Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer. 2010;10(12):878–89. https://doi.org/10.1038/nrc2961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Nomaguchi M, Fujita M, Miyazaki Y, Adachi A. Viral Tropism. Front Microbiol. 2012;3:281. https://doi.org/10.3389/fmicb.2012.00281.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Crow MS, Javitt A, Cristea LLM. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms. J Mol Biol. 2015;427(11):1995–2012. https://doi.org/10.1016/j.jmb.2015.02.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Law GL, Korth MJ, Benecke AG, Katze MG. Systems virology: host-directed approaches to viral pathogenesis and drug targeting. Nat Rev Microbiol. 2013;11(7):455–66. https://doi.org/10.1038/nrmicro3036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Schäfer G, Blumenthal MJ, Katz AA. Interaction of human tumor viruses with host cell surface receptors and cell entry. Viruses. 2015;7(5):2592–617. https://doi.org/10.3390/v7052592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Nowak MA, May RM. Viral dynamics: mathematical principles of immunology and viro-logy. Oxford, UK: Oxford University Press; 2001. p. 2–3. ISBN 0-19-850417-9.

    Google Scholar 

  132. Van Regenmortel MHV. The metaphor that viruses are living is alive and well, but it is no more than a metaphor. Stud Hist Phil Biol Biomed Sci. 2016;59:117–24. https://doi.org/10.1016/j.shpsc.2016.02.017.

    Article  Google Scholar 

  133. Lin CZ, Xiang GL, Zhu XH, Xiu LL, Sun JX, Zhang XY. Advances in the mechanisms of action of cancer-targeting oncolytic viruses. Oncol Lett. 2018;15(4):4053–60. https://doi.org/10.3892/ol.2018.7829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kuss-Duerkop SK, Westrich JA, Pyeon D. DNA tumor virus replication of host DNA methylation and its implications for immune evasion and oncogenesis. Viruses. 2018;10(2):E82. https://doi.org/10.3390/v10020082.

    Article  CAS  PubMed  Google Scholar 

  135. Jiang M, Imperiale MJ. Design starts: how small DNA viruses remodel the host nucleus. Futur Virol. 2012;7(5):445–59. https://doi.org/10.2217/FVL.12.38.

    Article  CAS  Google Scholar 

  136. Turnell AS, Grand RJ. DNA viruses and the cellular DNA-damage response. J Gen Virol. 2012;93(Pt 10):2076–97. https://doi.org/10.1099/vir.0.044412-0.

    Article  CAS  PubMed  Google Scholar 

  137. Saldivar JC, Cortez D, Cimprich KA. The essential kinase ATR: ensuring faithful duplication of a challenging genome. Nat Rev Mol Cell Biol. 2017;18(10):622–36. https://doi.org/10.1038/nrm.2017.67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhao J, Dang X, Zhang P, Nguyen LN, Cao D, Wang L, et al. Insufficiency of DNA repair enzyme ATM promotes naïve CD4 T-cell loss in chronic hepatitis C virus infection. Cell Discovery. 2018;4:16. https://doi.org/10.1038/s41421-018-0015-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. American Cancer Society (ACS). Cancer prevention and early detection facts and figures 2017–2017. Atlanta: American Cancer Society. 2017.

    Google Scholar 

  140. Seeger C, Mason WS. Molecular biology of hepatitis B virus infection. Virology. 2015;479–480:672–86. https://doi.org/10.1016/j.virol.2015.02.031.

    Article  CAS  PubMed  Google Scholar 

  141. Lamontagne RJ, Bagga S, Bouchard MJ. Hepatitis B virus molecular biology and pathogenesis. Hepatoma Res. 2016;2:163–86. https://doi.org/10.20517/2394-5079.2016.05.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Xu W, Yu J, Wong VW-S. Mechanism and predictions of HCC development in HBV infection. Best Pract Res Clin Gastroenterol. 2017;31(3):291–8. https://doi.org/10.1016/j.bpg.2017.04.011.

    Article  PubMed  Google Scholar 

  143. Levrero M, Zucman-Rossi J. Mechanism of HBV-induced hepatocellular carcinoma. J Hepatol. 2016;64(1 Suppl):S84–S101. https://doi.org/10.1016/j.jhep.2016.02.021.

    Article  CAS  PubMed  Google Scholar 

  144. De Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324(1):17–27. https://doi.org/10.1016/j.virol.2004.03.033.

    Article  CAS  PubMed  Google Scholar 

  145. Picconi MA, Alonio LV, García-Carrancá A, Lizano M, Cervantes-Vazquez G, Distefano AL, et al. Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix. Medicina (Buenos Aires). 2000;60(6):889–94.

    CAS  Google Scholar 

  146. Travasso CM, Anand M, Samarth M, Deshpande A, Kumar-Sinha C. Human papillomavirus genotyping by multiplex pyrosequencing in cervical cancer patients from India. J Biosci. 2008;33(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  147. Cal CM. El virus del papiloma humano. Cadernos de Atención Primaria. 2008;15(1):72–4.

    Google Scholar 

  148. Goering RV. Molecular epidemiology of nosocomial infection: analysis of chromosomal restriction fragment patterns by pulsed-field gel electrophoresis. Infect Control Hosp Epidemiol. 1993;14(10):595–600.

    Article  CAS  PubMed  Google Scholar 

  149. Chan SY, Bernard HU, Ratterree M, Birkebak TA, Faras AJ, Ostrow RS. Genomic diversity and evolution of papillomaviruses in rhesus monkeys. J Virol. 1997;71(7):4938–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Vanegas VA, Rubio AI, Bedoya AM, Sánchez GI. Estructura molecular y antigénica de la vacuna contra el virus de papiloma humano 16 (VPH 16). Acta Biológica Colombiana. 2008;13(3):37–48.

    Google Scholar 

  151. Yamada T, Wheeler CM, Halpern AL, Stewart AC, Hildesheim A, Jenison SA. Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. J Virol. 1995;69(12):7743–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Yamada T, Manos MM, Peto J, Greer CE, Munoz N, Bosch FX, Wheeler CM. Human papillomavirus type 16 sequence variation in cervical cancer: a worldwide perspective. J Virol. 1997;71(3):2463–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD, Sylla BS, et al. Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol. 2012;86(12):6855–61. https://doi.org/10.1128/JVI.00483-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Taylor ER, Morgan IM. A novel technique with enhanced detection and quantitation of HPV-16 E1- and E2-mediated DNA replication. Virology. 2003;315(1):103–9. https://doi.org/10.1016/S0042-6822(03)00588-9.

    Article  CAS  PubMed  Google Scholar 

  155. Okoye A, Cordano P, Taylor ER, Morgan IM, Everett R, Campo MS. Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2. Virus Res. 2005;108(1–2):1–14. https://doi.org/10.1016/j.virusres.2004.07.004.

    Article  CAS  PubMed  Google Scholar 

  156. International Agency for Research on Cancer (IARC). IARC monographs on the evaluation of carcinogenesis risks to humans. vol. 100B. IARC Press 2012. ISBN 978 92 832 1319 2. ISSN 1017-1606. Lyon, France.

    Google Scholar 

  157. Flores ER, Allen-Hoffman BL, Lee D, Sattler CA, Lambert PF. Establishment of the human papillomavirus type 16 (HPV-16) life cycle in an immortalized human foreskin keratinocyte cell line. Virology. 1999;262(2):344–54. https://doi.org/10.1006/viro.1999.9868.

    Article  CAS  PubMed  Google Scholar 

  158. Frazer IH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol. 2004;4(1):46–55. https://doi.org/10.1038/nri1260.

    Article  CAS  PubMed  Google Scholar 

  159. Polyomaviridae Study Group of the International on Taxonomy of viruses, Calvignac-Spencer S, Feltkamp MCW, Dauherty MD, Moens U, Ramqvist T, et al. A taxonomy update for the family polyomaviridae. Arch Virol. 2016;161(6):1739–50. https://doi.org/10.1007/s00705-016-2794-y.

    Article  CAS  Google Scholar 

  160. Liu W, MacDonald M, You J. Merkel cell polyomavirus infection and Merkel cell carcinoma. Curr Opin Virol. 2016;20:20–7. https://doi.org/10.1016/j.coviro.2016.07.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Bhart H, Solis M, Kack-Kack W, Soulier E, Velay A, Fafi-Kremer S. In vitro and in vivo models for the study of human polyomavirus infection. Viruses. 2016;8(10):292. https://doi.org/10.3390/v8100292.

    Article  CAS  Google Scholar 

  162. Wendzicki JA, Moore PS, Chang Y. Large T and small T antigens of Merkel cell polyomavirus. Curr Opin Virol. 2015;11:38–43. https://doi.org/10.1016/j.coviro.2015.01.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Spurgeon ME, Lambert PF. Merkel cell polyomavirus: a newly discovered human virus. Virology. 2013;435(1):118–30. https://doi.org/10.1016/j.virol.2012.09.029.

    Article  CAS  PubMed  Google Scholar 

  164. Cook DL, Frieling GW. Merkel cell carcinoma: a review and update on current concepts. Diagn Histopathol. 2016;22(4):127–33. https://doi.org/10.1016/j.mpdhp.2016.04.002.

    Article  Google Scholar 

  165. Van der Meijden E, Kazem S, Dargel CA, Vuren NV, Hensbergen PJ, MCW F. Characterization of T antigens, including middle T and alternative T, expressed by the human polyomavirus associated with trichodysplasia spinulosa. J Virol. 2015;89(18):9427–39. https://doi.org/10.1128/JVI.00911-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Shuda M, Kwun HJ, Feng H, Chang Y, Moore P. Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. J Clin Invest. 2011;121(9):3623–34. https://doi.org/10.1172/JCI46323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Esau D. Viral causes of lymphoma: the history of Epstein-Barr virus and human T-lymphotropic virus 1. Virology. 2017;8:1–5. https://doi.org/10.1177/1178122X17731772.

    Article  Google Scholar 

  168. International Agency for Research on Cancer (IARC). Section of infections – infections and cancer biology group. 2018a. http://www.iarc.fr/en/research-groups/ICB/index.php. Accessed 27 Mar 2018.

  169. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096–100. https://doi.org/10.1126/science.1152586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Kassem A, Schöpflin A, Diaz C, Weyers W, Stickeler E, Werner M, et al. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 2008;68(13):5009–13. https://doi.org/10.1158/0008-5472.CAN-08-0949.

    Article  CAS  PubMed  Google Scholar 

  171. Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, et al. T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A. 2008;105(42):16272–7. https://doi.org/10.1073/pnas.0806526105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Moore PS, Chang Y. Common commensal cancer viruses. PLoS Pathog. 2017;13(1):e1006078. https://doi.org/10.1371/journal.ppat.1006078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Mizuguchi Y, Takizawa T, Yoshida H, Uchida E. Dysregulated miRNA in progression of hepatocelular carcinoma; a systematic review. Hepatol Res. 2016;46(5):391–406. https://doi.org/10.1111/hepr.12606.

    Article  CAS  PubMed  Google Scholar 

  174. Yue D, Zhang Y, Cheng L, Ma J, Xi Y, Yang L, et al. Hepatitis B virus X protein (HBx) induced abnormalities of nucleic acid metabolism revealed by H-NMR-based metabonomics. Sci Rep. 2016;6(24430):1–13. https://doi.org/10.1038/srep24430.

    Article  CAS  Google Scholar 

  175. World Health Organization (WHO). Weekly epidemiological record. 2014;43(89):465–92. ISSN 0049-8114.

    Google Scholar 

  176. Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121(1):1–14. https://doi.org/10.1111/j.1365-2567.2007.02587.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Yuzhalin A, Kutikhin A. Interleukins in cancer biology: their heterogeneous role. Chapter 1–10, edited by Arseniy E. Yuzhalin Anton G. Kutikhin, Academic Press, Amsterdam, 2015. ISBN 9780128011218.

    Google Scholar 

  178. Read SA, Douglas MW. Virus induced inflammation and cancer development. Cancer Lett. 2014;345(2):174–81. https://doi.org/10.1016/j.canlet.2013.07.030.

    Article  CAS  PubMed  Google Scholar 

  179. Torres-Poveda K, Bahena-Román M, Madrid-González C, Burguete-García AI, Bermúdez-Morales VH, Peralta-Zaragoza O, et al. Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia. World J Clin Oncol. 2014;5(4):753–63. https://doi.org/10.5306/wjco.v5.i4.753.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Jeon S, Allen-Hoffmann BL, Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol. 1995;69(5):2989–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Zhou F, Leggatt GR, Frazer IH. Human papillomavirus 16 E7 protein inhibits interferon-γ-mediated enhancement of keratinocytes antigen processing and T-cell lysis. FEBS J. 2011;278(6):955–63. https://doi.org/10.1111/j.1742-4658.2011.08011.x.

    Article  CAS  PubMed  Google Scholar 

  182. Ren C, Cheng X, Lu B, Yang G. Activation of interleukin-6/signal transducer and activator of transcription 3 by human papillomavirus early proteins 6 induces fibroblast senescence to promote cervical tumourigenesis through autocrine and paracrine pathways in tumour microenvironment. Eur J Cancer. 2013;49(18):3889–99. https://doi.org/10.1016/j.ejca.2013.07.140.

    Article  CAS  PubMed  Google Scholar 

  183. Song D, Li H, Li H, Dai J. Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer. Oncol Lett. 2015;10(2):600–6. https://doi.org/10.3892/ol.2015.3295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Aggarwal R, Misra S, Guleria C, Suri V, Mangat N, Sharma M, et al. Characterization of toll-like receptor transcriptome in squamous cell carcinoma of cervix: a case-control study. Gynecol Oncol. 2015;138(2):358–62. https://doi.org/10.1016/j.ygyno.2015.05.029.

    Article  CAS  PubMed  Google Scholar 

  185. Bhat P, Mattarollo SR, Gosmann C, Frazer IH, Leggatt GR. Regulation of immune responses to HPV infection and during HPV-directed immunotherapy. Immunol Rev. 2011;239(1):85–98. https://doi.org/10.1111/j.1600-065X.2010.00966.x.

    Article  CAS  PubMed  Google Scholar 

  186. Bermúdez-Morales VH, Peralta-Zaragoza O, Alcocer-González JM, Moreno J, Madrid-Marina V. IL-10 expression is regulated by HPV E2 protein in cervical cancer cells. Mol Med Rep. 2011;4(2):369–75. https://doi.org/10.3892/mmr.2011.429.

    Article  CAS  PubMed  Google Scholar 

  187. Conesa-Zamora P. Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape. Gynecol Oncol. 2013;131(2):480–8. https://doi.org/10.1016/j.ygyno.2013.08.025.

    Article  CAS  PubMed  Google Scholar 

  188. Song SH, Lee JK, Seok OS, Saw HS. The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Gynecol Oncol. 2007;104(3):732–8. https://doi.org/10.1016/j.ygyno.2006.10.054.

    Article  CAS  PubMed  Google Scholar 

  189. Vandermark ER, Deluca KA, Gardner CR, Marker DF, Schreiner CN, Strickland DA, et al. Human papillomavirus type 16 E6 and E7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization. Virology. 2012;425(1):53–60. https://doi.org/10.1016/j.virol.2011.12.023.

    Article  CAS  PubMed  Google Scholar 

  190. Houben R, Angermeyer S, Haferkamp S, Aue A, Goebeler M, Schrama D, et al. Characterization of functional domains in the Merkel cell polyoma virus large T antigen. Int J Cancer. 2015;136(5):E290–300. https://doi.org/10.1002/ijc.29200.

    Article  CAS  PubMed  Google Scholar 

  191. Sauer CM, Haugg AM, Chteinberg E, Rennspiess D, Winnepenninckx V, Speel E-J, et al. Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma. Crit Rev Oncol Hematol. 2017;116:99–105. https://doi.org/10.1016/j.critrevonc.

    Article  CAS  PubMed  Google Scholar 

  192. Van der Meijden E, Feltkamp M. The human polyomavirus middle and alternative T-antigens: thoughts on roles and relevance to cancer. Front Microbiol. 2018;9:398. https://doi.org/10.3389/fmicb.2018.00398.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Wang RF, Wang H. Immune targets and neoantigens for cancer immunotherapy and precision medicine. Cell Res. 2017;27(1):11–37. https://doi.org/10.1038/cr.2016.155.

    Article  CAS  PubMed  Google Scholar 

  194. Obeid JM, Hu Y, Slingluff CL Jr. Vaccines, adjuvants and dendritic cell activators – current status and futures challenges. Semin Oncol. 2015;42(4):549–61. https://doi.org/10.1053/j.seminoncol.2015.05.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Ophir E, Bobisse S, Coukos G, Harari A, Kandalaft LE. Personalized approaches to active immunotherapy in cancer. Biochim Biophys Acta. 2016;1865(1):72–82. https://doi.org/10.1016/j.bbcan.2015.07.004.

    Article  CAS  PubMed  Google Scholar 

  196. Song Q, Zhang C-D, Wu X-H. Therapeutic cancer vaccines: from initial findings to pros-pects. Immunol Lett. 2018;196:11–21. https://doi.org/10.1016/j.imlet.2018.01.011.

    Article  CAS  PubMed  Google Scholar 

  197. Zamarin D, Postow MA. Immune checkpoint modulation: rationale design of combination strategies. Pharmacol Ther. 2015;150:23–32. https://doi.org/10.1016/j.pharmthera.2015.01.003.

    Article  CAS  PubMed  Google Scholar 

  198. Whiteside TL. Inhibiting the inhibitors: evaluating agents targeting cancer immuno-suppression. Expert Opin Biol Ther. 2010;10(7):1019–35. https://doi.org/10.1517/14712598.2010.48220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Handisurya A, Lázár S, Papay P, Primas C, Haitel A, Horvat R, et al. Anogenital human papillomavirus prevalence is unaffected by therapeutic tumour necrosis factor-alpha inhibition. Acta Derm Venereol. 2016;96(4):494–8. https://doi.org/10.2340/00015555-2298.

    Article  CAS  PubMed  Google Scholar 

  200. Werberich GM, Strava T, Vizioli C, Fernandes GDS. Human papillomavirus-induced cancer: late relapse in a patient treated with tumor necrosis factor-alpha inhibitor. J Global Oncol. 2016;3(3):275–7. https://doi.org/10.1200/JGO.2016.005835.

    Article  Google Scholar 

  201. Neuzillet C, Tijeras-Raballand A, Cohen R, Cros J, Faivre S, Raymond E, et al. Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 2015;147:22–31. https://doi.org/10.1016/j.pharmthera.2014.11.001.

    Article  CAS  PubMed  Google Scholar 

  202. Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature. 2003;424(6948):516–23. https://doi.org/10.1038/nature01850.

    Article  CAS  PubMed  Google Scholar 

  203. DeCarlo CA, Severini A, Edler L, Escott NG, Lambert PF, Ulanova M, et al. IFN-κ, a novel type I IFN, is undetectable in HPV-positive human cervical keratinocytes. Lab Investig. 2010;90(10):1482–91. https://doi.org/10.1038/labinvest.2010.95.

    Article  CAS  PubMed  Google Scholar 

  204. Cancer Research UK (CRUK). Other treatments. 2018. http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/other. Accessed 30 May 2018.

  205. Abdo J, Cornell DL, Mittal SK, Agrawal DK. Immunotherapy plus cryotherapy: potential augmented abscopal effect for advanced cancers. Front Oncol. 2018;8(85):1–16. https://doi.org/10.3389/fonc.2018.00085.

    Article  Google Scholar 

  206. Russell SJ, Peng K-W, Bell JC. Oncolytyc virotherapy. Nat Biotechnol. 2012;30(7):658–70. https://doi.org/10.1038/nbt.2287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Chaurasiya S, Chen NG, Warner SG. Oncolytic virotherapy versus cancer stem cells: a review of approaches and mechanisms. Cancers. 2018;10(4):E124. https://doi.org/10.3390/cancers10040124.

    Article  CAS  PubMed  Google Scholar 

  208. Liu Y, Sethi MS, Hinoue T, Schneider BG, Cherniack AD, Sanchez-Vega F, et al. Comparative molecular analysis of gastrointestinal adenocarcinomas. Cancer Cell. 2018;33(4):721–35. https://doi.org/10.1016/j.ccell.2018.03.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Saleh T, Shojaosadati SA. Multifunctional nanoparticles for cancer immunotherapy. Hum Vaccin Immunother. 2016;12(7):1863–75. https://doi.org/10.1080/21645515.2016.1147635.

    Article  PubMed  PubMed Central  Google Scholar 

  210. Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168–82. https://doi.org/10.1038/nri.2017.131.

    Article  CAS  PubMed  Google Scholar 

  211. Melief CJM, van Hall T, Arens R, Ossendorp F, van der Burg SH. Therapeutic cancer vaccines. J Clin Invest. 2015;125(9):3401–12. https://doi.org/10.1172/JCI80009.

    Article  PubMed  PubMed Central  Google Scholar 

  212. Palucka K, Banchereau J. Dendritic cell-based cancer therapeutic vaccines. Immunity. 2013;39(1):38–48. https://doi.org/10.1016/j.immuni.2013.07.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Sabado RL, Balan S, Bhardwaj N. Dendritic cell-based immunotherapy. Cell Res. 2017;27:74–95. https://doi.org/10.1038/cr.2016.157.

    Article  CAS  PubMed  Google Scholar 

  214. Shang N, Figini M, Shangguan J, Wang B, Sun C, Pan L, et al. Dendritic cells based immunotherapy. Am J Cancer Res. 2017;7(10):2091–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  215. Melief CJM. Cancer immunotherapy by dendritic cells. Immunity. 2008;29(3):372–83. https://doi.org/10.1016/j.immuni.2008.08.004.

    Article  CAS  PubMed  Google Scholar 

  216. Kumai T, Kobayashi H, Harabuchi Y, Celis E. Peptide vaccines in cancer – old concept revisited. Curr Opin Immunol. 2017;45:1–7. https://doi.org/10.1016/j.coi.2016.11.001.

    Article  CAS  PubMed  Google Scholar 

  217. Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine nanodisc for personalized cancer immunotherapy. Nat Mater. 2017;16(4):489–96. https://doi.org/10.1038/nmat4822.

    Article  CAS  PubMed  Google Scholar 

  218. Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang XY. Therapeutic cancer vaccines: past, present and future. Adv Cancer Res. 2013;119:421–75. https://doi.org/10.1016/B978-0-12-407190-2.00007-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Li L, Pretrovsky N. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 2016;15(3):313–29. https://doi.org/10.1586/14760584.2016.1124762.

    Article  CAS  PubMed  Google Scholar 

  220. Yang B, Jeang J, Yang A, Wu TC, Hung CF. DNA vaccine for cancer immunotherapy. Hum Vaccin Immunother. 2014;10(11):3153–64. https://doi.org/10.4161/21645515.2014.980686.

    Article  PubMed  Google Scholar 

  221. Guo P, Wang J, Liu J, Xia M, Li W. Macrophage immigration inhibitory factor promotes cell proliferation and inhibits apoptosis of cervical adenocarcinoma. Tumour Biol. 2015;36(7):5095–102. https://doi.org/10.1007/s13277-015-3161-4.

    Article  CAS  PubMed  Google Scholar 

  222. Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 2014;25(4):377–90. https://doi.org/10.1016/j.cytogfr.2014.07.018.

    Article  CAS  PubMed  Google Scholar 

  223. Soares KC, Rucki AA, Wu AA, Olino K, Xiao Q, Chai Y, et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T cell infiltration into pancreatic tumors. J Immunother. 2015;38(1):1–11. https://doi.org/10.1097/CJI.0000000000000062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Linch SN, Kasiewickz MJ, McNamara MJ, Hilgart-Martiszus IF, Farhad M, Redmond WL. Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice. Proc Natl Acad Sci U S A. 2016;113(3):E319–27. https://doi.org/10.1073/pnas.1510518113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119–27. https://doi.org/10.1056/NEJMoa1012863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Dutta R, Mahato RI. Recent advances in hepatocellular carcinoma therapy. Pharmacol Ther. 2017;173:106–17. https://doi.org/10.1016/j.pharmthera.2017.02.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Hochnadel I, Kossatz-Boehlert U, Jedicke N, Lenzen H, Manns MP, Yevsa T. Cancer vaccines and immunotherapeutic approaches in hepatobiliary and pancreatic. Hum Vaccin Immunother. 2017;13(12):2931–52. https://doi.org/10.1080/21645515.2017.1359362.

    Article  PubMed  PubMed Central  Google Scholar 

  228. Bann DV, Deschler DG, Goyal N. Novel immunotherapeutic approaches for head and neck squamous cell carcinoma. Cancers. 2016;8(10):E87. https://doi.org/10.3390/cancers8100087.

    Article  CAS  PubMed  Google Scholar 

  229. Tello TL, Coggshall K, Yom SS, Yu SS. Merkel cell carcinoma: an update and review: current and future therapy. J Am Acad Dermatol. 2018;78(3):445–54. https://doi.org/10.1016/j.jaad.2017.12.004.

    Article  PubMed  Google Scholar 

  230. Harms PW. Update on Merkel cell carcinoma. Clin Lab Med. 2017;37(3):485–501. https://doi.org/10.1016/j.cll.2017.05.004.

    Article  PubMed  Google Scholar 

  231. Delhalle S, Bode SFN, Balling E, Ollert M, He FQ. A roadmap towards personalized immunology. NPJ Syst Biol Appl. 2018;4(9):1–14. https://doi.org/10.1038/s41540-017-0045-9.

    Article  Google Scholar 

  232. Silva JM, Videira M, Gaspar R, Préat V, Florindo HF. Immune system targeting by biodegradable nanoparticles for cancer vaccines. J Control Release. 2013;168(2):179–99. https://doi.org/10.1016/j.jconrel.2013.03.010.

    Article  CAS  PubMed  Google Scholar 

  233. Sahin U, Türeci O. Personalized vaccines for cancer immunotherapy. Science. 2018;359(6382):1355–60. https://doi.org/10.1126/science.aar7112.

    Article  CAS  PubMed  Google Scholar 

  234. Zhang X, Sharma PK, Goedegebuure P, Gillanders WE. Personalized cancer vaccines: targeting the cancer mutanome. Vaccine. 2017;35(7):1094–100. https://doi.org/10.1016/j.vaccine.2016.05.073.

    Article  CAS  PubMed  Google Scholar 

  235. Yarchoan M, Johnson BA 3rd, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17(4):209–22. https://doi.org/10.1038/nrc.2016.154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Gruijl TD, van den Eertwegh AJM, Pinedo HM, Scheper RJ. Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunol Immunother. 2008;57(10):1569–77. https://doi.org/10.1007/s00262-008-0536-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Bencherif SA, Sands RW, Ali OA, Li WA, Lewin SA, Braschler TM, et al. Injectable cryogel-based whole cell cancer vaccines. Nat Commun. 2015;6:7556. https://doi.org/10.1038/ncomms8556.

    Article  CAS  PubMed  Google Scholar 

  238. Kandalaft LE, Chiang CL, Tanyi J, Motz G, Balint K, Mick R. A phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer. J Transl Med. 2013;11:149. https://doi.org/10.1186/1479-5876-11-149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Yang YW, Luo WH. Cellular biodistribution of polymeric nanoparticles in the immune system. J Control Release. 2016;227:82–93. https://doi.org/10.1016/j.jconrel.2016.02.011.

    Article  CAS  PubMed  Google Scholar 

  240. Bolhassani A, Javanzad S, Saleh T, Hashemi M, Aghasadeghi MR, Sadat SM. Polymeric nanoparticles: potent vector s for vaccine delivery targeting cancer and infectious diseases. Hum Vaccin Immunother. 2014;10(2):321–32. https://doi.org/10.4161/hv.26796.

    Article  CAS  PubMed  Google Scholar 

  241. Le Gall CM, Weiden J, Eggermont LJ, Figdor CG. Dendritic cells in cancer immunotherapy. Nat Mater. 2018;17:472–7. https://doi.org/10.1038/s41563-018-0093-6.

    Article  CAS  Google Scholar 

  242. Zhu M, Wang R, Nie G. Applications of nanomaterials as vaccine adjuvants. Hum Vaccin Immunother. 2014;10(9):2761–74. https://doi.org/10.4161/hv.29589.

    Article  PubMed  PubMed Central  Google Scholar 

  243. Zhu G, Lynn GM, Jacobson O, Chen K, Liu Y, Zhang H, et al. Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy. Nat Commun. 2017;8(1954):1–15. https://doi.org/10.1038/s41467-017-02191-y.

    Article  CAS  Google Scholar 

  244. Fecek RJ, Storkus WJ. Combination strategies to enhance the potency of monocyte-derived dendritic cell-based cancer vaccines. Immunotherapy. 2016;8(10):1205–18. https://doi.org/10.2217/imt-2016-0071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Koido S. Dendritic-tumor fusion cell-based cancer vaccines. Int J Mol Sci. 2016;17(6):E828. https://doi.org/10.3390/ijms17060828.

    Article  CAS  PubMed  Google Scholar 

  246. Castiglione F, Bernaschi M. Epitope screening and cell cooperation in the immune response. Intelligent Systems, Modelling and Simulations (ISMS). Proceedings – 2011 2nd International Conference on Intelligence Systems, Modeling and Simulations. ISMS. 2011 Feb;127–132. https://doi.org/10.1109/ISMS.2011.30.

  247. Daudi J. An overview of application of artificial immune system in swarm robotic systems. Adv Robotics Automat. 2015;4:127. https://doi.org/10.4172/2168-9695.1000127.

    Article  Google Scholar 

  248. Zeeshan M, Javed H, Haider A, Khan A. An immunology inspired flow control attack detection using negative selection with r-contiguous bit matching for wireless sensor networks. Int J Distrib Sensor Networ 2015;11(11):1–7. doi:https://doi.org/10.1155/2015/169654.

    Article  Google Scholar 

  249. Khan MT, de Silva, CW. Autonomous fault tolerance multi-robot cooperation using artificial immune system. Automation and Logistics. ICAL 2008. IEEE International Conference on 2008. 2008 Sep;623–8. https://doi.org/10.1109/ICAL.2008.4636225.

  250. Nigam D, Kumar V. Artificial immune system: a potential tool to handle bioinformatics issues. Int J Artif Intell Knowl Discov. 2012;2(1):1–5.

    Google Scholar 

  251. Saybani MR, Shamshirband S, Hormozi SG, Wah TY, Aghabozorgi S, Pourhoseingholi MA, et al. Diagnosing tuberculosis with a novel support vector machine-based artificial immune system recognition system. Iran Red Crescent Med J. 2015;17(4):e24557. https://doi.org/10.5812/ircmj.17(4)2015.24557.

    Article  PubMed  PubMed Central  Google Scholar 

  252. Onomza WV, Alhassan J, Alelere M, Tunde A. Development of secure plus antivirus with the artificial immune system model. Int J Innov Technol Res. 2015;3(2):1882–96.

    Google Scholar 

  253. Rai N, Singh A. Improved clonal selection algorithm (ICLONALG). Int J Current Eng Technol. 2015;5(4):2459–64.

    Google Scholar 

  254. Ali NIM, Malek MA, Ismail AR. Immune network algorithm in monthly streamflow prediction at Johor river. ARPN J Eng Appl Sci. 2015;10(3):1352–6.

    Google Scholar 

  255. Zeng J. Computer malicious executables detection based on real-valued negative selection algorithm. Appl Math Inform Sci. 2015;9(2):1089–94. https://doi.org/10.12785/amis/090260.

    Article  Google Scholar 

  256. Liò P, Miglino O, Nocosia G, Nolfi S, Pavone M. Advances in artificial life: synthesis and simulation of living systems: editorial. Artif Life. 2015;21(4):395–7. https://doi.org/10.1162/ARTL_e_00189.

    Article  PubMed  Google Scholar 

  257. Langton CG. Artificial Life: proceedings of an interdisciplinary workshop on the synthesis and simulation of living systems, held September, 1987, in Los Alamos, New Mexico, Santa Fe Institute Studies in the Sciences of Complexity. 1989; vol VI. Addison-Wesley.

    Google Scholar 

  258. Ray TS. An evolutionary approach to synthetic biology: zen and the art of creating life. Artif Life. 1994;1(1/2):195–226.. MIT Press. https://doi.org/10.1162/artl.1993.1.179.

    Article  Google Scholar 

  259. Aguilar W, Santamaría-Bonfil G, Froese T, Gershenson C. The past, present, and future for artificial life. Front Robotics AI. 2014;1:8. https://doi.org/10.3389/frobt.2014.00008.

    Article  Google Scholar 

  260. Williams RA. Lesson learned on development and application of agent-based models of complex dynamical systems. Simul Model Pract Theory. 2018;83:201–12. https://doi.org/10.1016/j.simpat.2017.11.001.

    Article  Google Scholar 

  261. Komosinski M, Adamatzky A, editors. Artificial life models in software. Second ed: Springer; 2009. https://doi.org/10.1007/978-1-84882-285-6.

    Google Scholar 

  262. Bauer AL, Beauchemin CAA, Perelson AS. Agent-based modeling of host-pathogen systems: the successes and challenges. Inf Sci. 2009;179(10):1379–89. https://doi.org/10.1016/j.ins.2008.11.012.

    Article  Google Scholar 

  263. Elkalaawy N, Wassal A. Methodologies for the modeling and simulation of biochemical networks, illustrated for signal transduction pathways: a primer. Biosystems. 2015;129:1–18. https://doi.org/10.1016/j.biosystems.2015.01.008.

    Article  CAS  PubMed  Google Scholar 

  264. Helbing D, Balietti S. How to do agent-based simulations in the future: from modeling social mechanism to emergent phenomena and interactive systems design. Chapter 2: agent-based modeling of the book Social Self-Organization. Springer, Berlin. 2012 Feb;25–70. https://doi.org/10.1007/978-3-642-24004-1 2.

    Google Scholar 

  265. An G, Mi Q, Dutta-Moscato J, Vodovotz Y. Agent-based models in translational systems biology. WIREs Syst Biol Med. 2009;1(2):159–71. https://doi.org/10.1002/wsbm.45.

    Article  CAS  Google Scholar 

  266. Hwang M, Garbey M, Berceli SA, Tran-Son-Tay R. Rule-based simulation of multi-cellular biological systems – a review of modeling techniques. Cell Mol Bioeng. 2009;2(3):285–94. https://doi.org/10.1007/s12195-009-0078-2.

    Article  PubMed  Google Scholar 

  267. North MJ, Macal CM. Foundations of and recent advances in artificial life modeling with repast 3 and repast symphony. In: Komosinski M, Adamatzky A, editors. Artificial life models in software. London: Springer; 2009;. Chapter 2. p. 37–60.

    Chapter  Google Scholar 

  268. Pezzulo G, Levin M. Top-down models in biology: explanation and control of complex living systems above the molecular level. J R Soc Interface. 2016;13(24):1–16. https://doi.org/10.1098/rsif.2016.0555.

    Article  Google Scholar 

  269. Loscalzo J, Barabasi AL. Systems biology and future of medicine. Wiley Interdiscip Rev Syst Biol Med. 2011;3(6):619–27. https://doi.org/10.1002/wsbm.144.

    Article  PubMed  PubMed Central  Google Scholar 

  270. Seiden PE, Celada F. A model for simulating cognate recognition and response in the immune system. J Theor Biol. 1992;158(3):329–57. https://doi.org/10.1016/S0022-5193(05)80737-4.

    Article  CAS  PubMed  Google Scholar 

  271. Celada F, Seiden PE. Affinity maturation and hypermutation in a simulation of the humoral immune response. Eur J Immunol. 1996;26(6):1350–8. https://doi.org/10.1002/eji.1830260626.

    Article  CAS  PubMed  Google Scholar 

  272. Meier-Schellersheim M, Mack G. SIMMUNE, a tool for simulating and analyzing immune system behavior. Cornell University Library. 1999 Mar; arXiv:cs/9903017v1.

  273. Bernaschi M, Castiglione F. Design and implementation of an immune system simulator. Comput Biol Med. 2001;31(5):303–31. https://doi.org/10.1016/S0010-4825(01)00011-7.

    Article  CAS  PubMed  Google Scholar 

  274. Puzone R, Kohler B, Seiden P, Celada F. IMMSIM, a flexible model for in machina expe-riments on immune system responses. Futur Gener Comput Syst. 2002;18(7):961–72. https://doi.org/10.1016/S0167-739X(02)00075-4.

    Article  Google Scholar 

  275. Pappalardo F, Lollini PL, Castiglione F, Motta S. Modeling and simulation of cancer immunoprevention vaccine. Bioinformatics. 2005;21(12):2891–7. https://doi.org/10.1093/bioinformatics/bti426.

    Article  CAS  PubMed  Google Scholar 

  276. Castiglione F, Bernaschi M, Succi S. Simulating the immune response on a distributed parallel computer. Int J Modern Phys C. 1997;8(3):527–45. https://doi.org/10.1142/S0129183197000424.

    Article  Google Scholar 

  277. Bernaschi M, Castiglione F. Selection of escape mutants from immune recognition during HIV infection. Immunol Cell Biol. 2002 Jun;80(3):307–313. https://doi.org/10.1046/j.1440-1711.2002.01082.

  278. Bandini S, Mauri G, Vizzari G. Supporting action-at-a-distance in situated cellular agents. Fundamenta Informaticae. 2006;69(3):251–71.

    Google Scholar 

  279. Baldazzi V, Castiglione F, Bernaschi M. An enhanced agent based model of the immune system response. Cell Immunol. 2006;244(2):77–9. https://doi.org/10.1016/j.cellimm.2006.12.006.

    Article  CAS  PubMed  Google Scholar 

  280. Castiglione F, Duca K, Jarrah A, Laubenbacher R, Hochberg D, Thorley-Lawson D. Simulating epstein–barr virus infection with C-ImmSim. Bioinformatics. 2007;23(11):1371–7. https://doi.org/10.1093/bioinformatics/btm044.

    Article  CAS  PubMed  Google Scholar 

  281. Mata J, Cohn M. Cellular automata-based modeling program: synthetic immune system. Immunol Rev. 2007;216(1):198–212. https://doi.org/10.1111/j.1600-065X.2007.00511.x.

    Article  PubMed  Google Scholar 

  282. Maeda K, Sakama C. Identifying cellular automata rules. J Cell Autom. 2007;2(1):1–20.

    Google Scholar 

  283. Folcik VA, An GC, Orosz CG. The basic immune simulator: an agent-based model to study the interactions between innate and adaptive immunity. Theor Biol Med Model. 2007;4(39):1–18. https://doi.org/10.1186/1742-4682-4-39.

    Article  CAS  Google Scholar 

  284. Dréau D, Dimitre S, Ted C, Mirsad H. An gent-based model of solid tumor progression. In: Rajasekaran S, editor. Bioinformatics and Computational Biology. BiCoB 2009. Lecture Notes in Computer Science. 2009;5462. Springer, Berlin, Heidelberg. doi:https://doi.org/10.1007/978-3-642-00727-9_19.

    Chapter  Google Scholar 

  285. De Pillis LG, Mallet DG, Radunskaya AE. Spatial tumor-immune modeling. Comput Math Methods Med. 2006;7(2–3):159–76. https://doi.org/10.1080/10273660600968978.

    Article  Google Scholar 

  286. Sneddon M, Faeder JR, Emonet T. Efficient modeling, simulation and coarse-graining of biological complexity with NFsim. Nat Methods. 2011;8(2):177–83. https://doi.org/10.1038/nmeth.1546.

    Article  CAS  PubMed  Google Scholar 

  287. Wendelsdorf KV, Alam M, Bassaganya-Riera J, Bisset K, Eubank S, Hontecillas R, et al. Enteric immunity simulator: a tool for in silico study of gastroenteric infections. IEEE Trans Nanobioscience. 2012;11(3):273–88. https://doi.org/10.1109/TNB.2012.2211891.

    Article  PubMed  PubMed Central  Google Scholar 

  288. Barret CL, Bisset KR, Eubank SG, Feng X, Marathe MV. Episimdemics: an efficient algorithm for simulating the spread of infectious disease over large realistic social networks. In: SC’2008: Proceedings of the 2008 ACM/IEEE Conference on Supercomputing. 2008 Nov;1–12. https://doi.org/10.1109/SC.2008.5214892.

  289. Kim PS, Lee PP. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach. PLoS Comput Biol. 2012;8(10):e1002742. https://doi.org/10.1371/journal.pcbi.1002742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  290. Mallet DG, De Pillis LG. A cellular automata model of tumor-immune system interactions. J Theor Biol. 2006;239(3):334–50. https://doi.org/10.1016/j.jtbi.2005.08.002.

    Article  CAS  PubMed  Google Scholar 

  291. Pappalardo F, Forero IM, Pennisi M, Palazon A, Melero I, Motta S. SimB16: modeling induced immune system response against B16-melanoma. PLoS One. 2011;6(10):e26523. https://doi.org/10.1371/journal.pone.0026523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  292. Von Eichborn J, Woelke AL, Castiglione F, Preissner R. VaccImm: simulating peptide vaccination in cancer therapy. BioMed Central Bioinform. 2013;14(127):1–8. https://doi.org/10.1186/1471-2105-14-127.

    Article  CAS  Google Scholar 

  293. Santos J, Monteagudo A. Analysis of behavior transitions in tumour growth using a cellular automaton simulation. IET Syst Biol. 2015;9(3):75–87. https://doi.org/10.1049/iet-syb.2014.0015.

    Article  PubMed  PubMed Central  Google Scholar 

  294. Shahmoradi S, Rahatabad FN, Maghooli K. A stochastic cellular automata model of growth of avascular tumor with immune response and immunotherapy. Inform Med Unlocked. 2018; https://doi.org/10.1016/j.imu.2018.06.008.

    Article  Google Scholar 

  295. Boondireck A, Lenbury Y, Wong-Ekkabut J, Triampo W, Tang IM, Picha P. A stochastic model of cancer growth with immune response. J Korean Phys Soc. 2006;49(4):1652–66.

    Google Scholar 

  296. Bezzi M, Celada F, Ruffo S, Seiden PE. The transition between immune and disease states in a cellular automaton model of clonal immune response. Phys A Stat Mech Its Appl. 1997;245(1–2):145–63. https://doi.org/10.1016/S0378-4371(97)00290-2.

    Article  CAS  Google Scholar 

  297. Celada F, Seiden P. Modeling immune cognition. IEEE International Conference on Systems, Man, and Cybernetics. San Diego, CA, USA. 1998 Oct; vol. 4, p. 3787–3792. https://doi.org/10.1109/ICSMC.1998.726677.

  298. Kleinstein SH, Seiden PE. Simulating the immune system. Comput Sci Eng. 2000;2(4):69–77. https://doi.org/10.1109/5992.852392.

    Article  CAS  Google Scholar 

  299. Kohler B, Puzone R, Seiden PE, Celada F. A systematic approach to vaccine complexity using an automaton model of the cellular and humoral immune system. I. Viral characteristics and polarized responses. Vaccine. 2000;19(7–8):862–76. https://doi.org/10.1016/S0264-410X(00)00225-5.

    Article  CAS  PubMed  Google Scholar 

  300. Stewart JJ, Agosto H, Litwin S, Welsh JD, Shlomchik M, Weigert M, Seiden PE. A solution to the rheumatoid factor paradox: pathologic rheumatoid factors can be tolerized by competition with natural rheumatoid factors. J Immunol. 1997;159(4):1728–38.

    CAS  PubMed  Google Scholar 

  301. Bardi JS. New NIAID program aims to model immune responses and key infectious diseases. NIH/National Institute of Allergy and Infectious Diseases 2012 Jul. http://www.nih.gov/news/pr/jul2006/niaid-12.htm. Accessed 8 Sep 2012.

  302. Langman RE, Mata J, Cohn M. A computerized model for the self-non-self discrimination at the level of the Th (Th genesis). II. The behavior of the system upon encounter with non-self antigens. Int Immunol. 2003;15(5):593–609. https://doi.org/10.1093/intimm/dxg059.

    Article  CAS  PubMed  Google Scholar 

  303. Emerson A, Rossi E. ImmunoGrid – the virtual human immune system project. Stud Health Technol Inform. 2007;126:87–92.

    PubMed  Google Scholar 

  304. Halling-Brown M, Pappalardo F, Rapin N, Zhang P, Alemani D, Emerson A, et al. ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale. Phil Trans R Soc A. 2010;368:2799–815. https://doi.org/10.1098/rsta.2010.0067.

    Article  PubMed  Google Scholar 

  305. Strain MC, Richman DD, Wong JK, Levine H. Spatiotemporal dynamics of HIV propagation. J Theor Biol. 2002;218(1):85–96. https://doi.org/10.1006/jtbi.2002.3055.

    Article  CAS  PubMed  Google Scholar 

  306. Segovia-Juarez JL. Ganguli S, Kirschner D. identifying control mechanisms of granuloma formation during M. tuberculosis infection using an agent-based model. J Theor Biol. 2004;231(3):357–76. https://doi.org/10.1016/j.jtbi.2004.06.031.

    Article  CAS  PubMed  Google Scholar 

  307. Beauchemin C. MASyV: A Multi-Agent System Visualization program. Free open-source GNU GPL software available online on SourceForge.net. http://masyv.sourceforge.net/. Accessed 9 Sep 2012.

  308. Motta S, Castiglione F, Lollini P, Pappalardo F. Modelling vaccination schedules for a cancer immunoprevention vaccine. Immunome Res. 2005;1(5):1–18. https://doi.org/10.1186/1745-7580-1-5.

    Article  CAS  Google Scholar 

  309. Alarcon T, Byrne HM, Maini PK. A multiple scale model for tumor growth. Society for Industrial and Applied Mathematics. Multiscale Model Simul. 2005;3(2):440–75. https://doi.org/10.1137/040603760.

    Article  CAS  Google Scholar 

  310. Zhang Y, Wallace DL, de Lara CM, Ghattas H, Asquith B, Worth A, et al. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology. 2007;121(2):258–65. https://doi.org/10.1111/j.1365-2567.2007.02573.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  311. Warrender C, Forrest S, Koster F. Modeling intercellular interactions in early Mycobaterium infection. Bull Math Biol. 2006;68(8):2233–61. https://doi.org/10.1007/s11538-006-9103-y.

    Article  PubMed  Google Scholar 

  312. Shapiro M, Duca KA, Lee K, Delgado-Eckert E, Hawkins J, Jarrah AS, et al. A virtual look at Epstein–Barr virus infection: simulation mechanism. J Theor Biol. 2008;252(4):633–48. https://doi.org/10.1016/j.jtbi.2008.01.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  313. Beauchemin C, Forrest S, Koster FT. Modeling influenza viral dynamics in tissue. In: Bersini H, Carneiro J, editors. Artificial immune systems. ICARIS 2006. Lecture notes in computer science, vol. 4163. Berlin: Springer; 2006. p. 23–36. https://doi.org/10.1007/11823940_3.

    Chapter  Google Scholar 

  314. Ebeling W, Schweitzer F. Swarms of particle agents with harmonic interactions. Theory Biosci. 2001;120(3–4):207–24. https://doi.org/10.1007/s12064-001-0019-7.

    Article  Google Scholar 

  315. Macal CM, North MJ. Tutorial on agent-based modeling and simulation part 2: how to model with agents. Simulation Conference 2006, WSC 06. Proceedings of the 38th conference on winter simulation. IEEE. 2006 Dec; pp.73–83. ISBN:1–4244–0501-7.

    Google Scholar 

  316. Baird L, Fagin B. Conserved energy functions for cellular automata: finding nontrivials faster through a complete theory of the trivials. J Cell Autom. 2012;7(2):115–50.

    Google Scholar 

  317. Escobar-Ospina ME, Gómez-Perdomo J. A growth model of human papillomavirus type 16 designed from cellular automata and agent-based models. Artif Intell Med. 2013;57(1):31–47. https://doi.org/10.1016/j.artmed.2012.11.001.

    Article  PubMed  Google Scholar 

  318. De Silva N, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015;15(3):137–48. https://doi.org/10.1038/nri3804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  319. Hwang JK, Alt FW, Yeap LS. Related mechanisms of antibody somatic hypermutation and class switch recombination. Microbiol Spectr. 2015;3(1):MDNA3-0037-2014. https://doi.org/10.1128/microbiolspec.MDNA3-0037-2014.

    Article  CAS  PubMed  Google Scholar 

  320. Kurosaki T, Kometani K, Ise W. Memory B cells. Nat Rev Immunol. 2015;15(3):149–59. https://doi.org/10.1038/nri3802.

    Article  CAS  PubMed  Google Scholar 

  321. Sen B, Johnson FM. Regulation of Src family kinases in human cancers. J Signal Transduc. 2011;865819:1–14. https://doi.org/10.1155/2011/865819.

    Article  CAS  Google Scholar 

  322. Railsback SF, Lytinen SL, Jackson SK. Agent-based simulation platforms: review and development recommendations. SIMULATION. 2006;82(9):609–23. https://doi.org/10.1177/0037549706073695.

    Article  Google Scholar 

  323. Abar S, Theodoropoulos GK, Lemarinier P, O’Hare GMP. Agent based modelling and simulation tools: a review of the state-of-art software. Comput Sci Rev. 2017;24:13–33. https://doi.org/10.1016/j.cosrev.2017.03.001.

    Article  Google Scholar 

  324. Hu C, Mao X, Li M, Zhu Z. Organization-based agent-oriented programming: model, mechanisms, and language. Front Comp Sci. 2014;8(1):33–51. https://doi.org/10.1007/s11704-013-2345-6.

    Article  Google Scholar 

  325. Ackley DH, Ackley ES. The ulam programming language for artificial life. Artif Life. 2016;22(4):431–50. https://doi.org/10.1162/ARTL_a_00212.

    Article  PubMed  Google Scholar 

  326. Yan Q, Li M, Liu Q, Li F, Zhu B, Wang J, et al. Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV). Sci Rep. 2016;6(28776):1–11. https://doi.org/10.1038/srep28776.

    Article  CAS  Google Scholar 

  327. Yi Z, Lin WW, Stunz LL, Bishop GA. Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions. Cytokine Growth Factor Rev. 2014;25(2):147–56. https://doi.org/10.1016/j.cytogfr.2013.12.002.

    Article  CAS  PubMed  Google Scholar 

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Escobar-Ospina, M.E., Gómez, J. (2019). Artificial Life and Therapeutic Vaccines Against Cancers that Originate in Viruses. In: Shapshak, P., et al. Global Virology III: Virology in the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-030-29022-1_8

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