Skip to main content

Oncolytic Virotherapy and the Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1036))

Abstract

Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using “targeted and armed” viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the immune system—such as cytokines and chemokines. In addition, oncolytic viruses can induce anti-vascular effects and disrupt the extracellular matrix to improve viral spread within the tumor. Oncolytic viruses also improve crosstalk between fibroblasts, cytokine-induced killer cells, and cancer cells within the microenvironment, leading to enhanced tumor cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  1. Sampath P, Thorne SH. Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy. Oncolytic Virother. 2015;4:75–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Guo ZH, Thorne SH, Barlett DL. Oncolytic virotherapy: molecular targets in tumor-selective replication and carrier cell-mediated delivery of oncolytic viruses. Biochim Biophys Acta. 2008;1785(2):217–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Kirn DH, Thorne SH. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer. 2009;9(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  4. Guo ZS, Liu Z, Bartlett DL. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol. 2014;4:74.

    PubMed  PubMed Central  Google Scholar 

  5. Miyamoto S, Inoue H, Nakamura T, et al. Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma. Cancer Res. 2012;72:2609–21.

    Article  CAS  PubMed  Google Scholar 

  6. Donnelly OG, Errington-Mais F, Steele L, et al. Measles virus causes immunogenic cell death in human melanoma. Gene Ther. 2013;20:7–15.

    Article  CAS  PubMed  Google Scholar 

  7. Guo ZS, Naik A, O’Malley ME, et al. The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2. Cancer Res. 2005;65:9991–8.

    Article  CAS  PubMed  Google Scholar 

  8. John LB, Howland LJ, Flynn JK, et al. Oncolytic virus and anti-4-1BB combination therapy elicits strong anti-tumor immunity against established cancer. Cancer Res. 2012;72:1651–60.

    Article  CAS  PubMed  Google Scholar 

  9. Whilding LM, Archibald KM, Kulbe H, et al. Vaccinia virus induces programmed necrosis in ovarian cancer cells. Mol Ther. 2013;21:2074–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Angelova AL, Grekova SP, Heller A, et al. Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV and gemcitabine in pancreatic cancer. J Virol. 2014;88(10):5263–76.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Liikanen I, Ahtiainen L, Hirvinen ML, et al. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther. 2013;21:1212–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Endo Y, Sakai R, Ouchi M, et al. Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation. Oncogene. 2008;27:2375–81.

    Article  CAS  PubMed  Google Scholar 

  13. Moehler M, Zeidler M, Schede J, et al. Oncolytic parvovirus H1 induces release of heat-shock protein HSP72 in susceptible human tumor cells but may not affect primary immune cells. Cancer Gene Ther. 2003;10:477–80.

    Article  CAS  PubMed  Google Scholar 

  14. Grekova S, Aprahamian M, Giese N, et al. Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent. Cancer Biol Ther. 2010;10:1280–9.

    Article  CAS  PubMed  Google Scholar 

  15. Grekova SP, Raykov Z, Zawatzky R, et al. Activation of a glioma-specific immune response by oncolytic parvovirus minute virus of mice infection. Cancer Gene Ther. 2012;19:468–75.

    Article  CAS  PubMed  Google Scholar 

  16. Radic M, Marion T, Monestier M. Nucleosomes are exposed at the cell surface in apoptosis. J Immunol. 2004;172:6692–700.

    Article  CAS  PubMed  Google Scholar 

  17. Uratsuji H, Tada Y, Kawashima T, et al. P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. J Immunol. 2012;188:436–44.

    Article  CAS  PubMed  Google Scholar 

  18. Elankumaran S, Rockemann D, Samal SK. Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J Virol. 2006;80:7522–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Meng C, Zhou Z, Jiang K, Yu S, Jia L, Wu Y, et al. Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication. Arch Virol. 2012;157:1011–8.

    Article  CAS  PubMed  Google Scholar 

  20. Washburn B, Schirrmacher V. Human tumor cell infection by Newcastle disease virus leads to upregulation of HLA and cell adhesion molecules and to induction of interferons, chemokines and finally apoptosis. Int J Oncol. 2002;21:85–93.

    CAS  PubMed  Google Scholar 

  21. Fournier P, Arnold A, Wilden H, Schirrmacher V. Newcastle disease virus induces pro-inflammatory conditions and type I interferon for counter-acting Treg activity. Int J Oncol. 2012;40:840–50.

    CAS  PubMed  Google Scholar 

  22. Zamarin D, Holmgaard RB, Subudhi SK, et al. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6:226–32.

    Article  Google Scholar 

  23. Errington F, Steele L, Prestwich R, et al. Reovirus activates human dendritic cells to promote innate antitumor immunity. J Immunol. 2008;180:6018–26.

    Article  CAS  PubMed  Google Scholar 

  24. Diaconu I, Cerullo V, Hirvinen ML, et al. Immune response is an important aspect of the antitumor effect produced by a CD40L-encoding oncolytic adenovirus. Cancer Res. 2012;72:2327–38.

    Article  CAS  PubMed  Google Scholar 

  25. Workenhe ST, Simmons G, Pol JG, et al. Immunogenic HSV-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy. Mol Ther. 2014;22:123–31.

    Article  CAS  PubMed  Google Scholar 

  26. Borde C, Barnay-Verdier S, Gaillard C, et al. Stepwise release of biologically active HMGB1 during HSV-2 infection. PLoS One. 2011;6:e16145. https://doi.org/10.1371/journal.pone.0016145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Workenhe ST, Pol JG, Lichty BD, et al. Combining oncolytic HSV-1 with immunogenic cell death-inducing drug mitoxantrone breaks cancer immune tolerance and improves therapeutic efficacy. Cancer Immunol Res. 2013;1:309–19.

    Article  CAS  PubMed  Google Scholar 

  28. Worschech A, Haddad D, Stroncek DF, et al. The immunological aspects of poxvirus oncolytic therapy. Cancer Immunol Immunother. 2009;58(9):1355–62.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Prestwich RJ, Errington F, Diaz RM, et al. The case of oncolytic viruses versus the immune system: waiting on the judgment of Solomon. Hum Gene Ther. 2009;20(10):1119–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bartlett DL, Liu Z, Sathaiah M, et al. Oncolytic viruses as therapeutic cancer vaccines. Mol Cancer. 2013;12:103.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim JH, Oh JY, Park BH, et al. Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol Ther. 2006;14(3):361–70.

    Article  CAS  PubMed  Google Scholar 

  32. Thorne SH. Immunotherapeutic potential of oncolytic vaccinia virus. Immunol Res. 2011;50(23):286–93.

    Article  CAS  PubMed  Google Scholar 

  33. Kirn DH, Wang Y, Le Boeuf F, et al. Targeting of interferon-beta to produce a specific, multi-mechanistic oncolytic vaccinia virus. PLoS Med. 2007;4(12):2001–12.

    Article  CAS  Google Scholar 

  34. Grigg P, Titong A, Jones LA, et al. Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics. Proc Natl Acad Sci U S A. 2013;110(38):15407–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chen H, Sampath P, Hou W, Thorne SH. Regulating Cytokine Function Enhances Safety and Activity of Genetic Cancer Therapies. Mol Ther. 2013;21(1):167–74.

    Article  CAS  PubMed  Google Scholar 

  36. Li J, O’Malley M, Urban J, et al. Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer. Mol Ther. 2011;19(4):650–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wang LC, Lynn RC, Cheng G, et al. Treating tumors with a vaccinia virus expressing IFN-β illustrates the complex relationships between oncolytic ability and immunogenicity. Mol Ther. 2012;20(4):736–48.

    Article  CAS  PubMed  Google Scholar 

  38. Cerullo V, Diaconu I, Romano V, et al. An oncolytic adenovirus enhanced for toll-like receptor 9 stimulation increases antitumor immune responses and tumor clearance. Mol Ther. 2012;20(11):2076–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Albelda SM, Thorne SH. Giving oncolytic vaccinia virus more BiTE. Mol Ther. 2014;22(1):6–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gil M, Komorowski MP, Seshadri M, et al. CXCL12/CXCR4 blockade by oncolytic virotherapy inhibits ovarian cancer growth by decreasing immunosuppression and targeting cancer-initiating cells. J Immunol. 2014;193(10):5327–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dias JD, Hemminki O, Diaconu I, et al. Targeted cancer immunotherapy with oncolytic adenovirus coding for a fully human monoclonal antibody specific for CTLA-4. Gene Ther. 2012;19(10):988–98.

    Article  CAS  PubMed  Google Scholar 

  42. Rojas JJ, Sampath P, Hou W, Thorne SH. Defining effective combinations of immune checkpoint blockade and oncolytic virotherapy. Clin Cancer Res. 2015;21(24):5543–51.

    Google Scholar 

  43. Wali A, Strayer DS. Infection with vaccinia virus alters regulation of cell cycle progression. DNA Cell Biol. 1999;18:837–43.

    Article  CAS  PubMed  Google Scholar 

  44. Ottolino-Perry, K., Acuna, SA, Angarita, FA, et al. Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer. Mol Oncol. 2015;9(8):1539–52. https://doi.org/10.1016/j.molonc.2015.04.009.

  45. Huang B, Sikorski R, Kirn DH, Thorne SH. Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1. Gene Ther. 2011;18:164–72.

    Article  CAS  PubMed  Google Scholar 

  46. Nishio N, Diaconu I, Liu H, et al. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors. Cancer Res. 2014;74(18):5195–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Melcher A, Paroto K, Rooney CM, Bell JC. Thunder and lightening: Immunotherapy and oncolytic viruses collide. Mol Ther. 2011;19(6):1008–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sobol PT, Boudreau JE, Stephenson K, et al. Adaptive antiviral immunity is a determinant of the therapeutic success of oncolytic virotherapy. Mol Ther. 2011;19:335–44.

    Article  CAS  PubMed  Google Scholar 

  49. Benencia F, Courrèges MC, Fraser NW, Coukos G. Herpes virus oncolytic therapy reverses tumor immune dysfunction and facilitates tumor antigen presentation. Cancer Biol Ther. 2008;7:1194–205.

    Article  CAS  PubMed  Google Scholar 

  50. Benencia F, Courrèges MC, Conejo-García JR, et al. HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol Ther. 2005;12:789–802.

    Article  CAS  PubMed  Google Scholar 

  51. Todo T, Martuza RL, Rabkin SD, Johnson PA. Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci U S A. 2001;98:6396–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li H, Dutuor A, Tao L, et al. Virotherapy with a type 2 herpes simplex virus-derived oncolytic virus induces potent antitumor immunity against neuroblastoma. Clin Cancer Res. 2007;13:316–22.

    Article  CAS  PubMed  Google Scholar 

  53. Li H, Dutuor A, Fu X, Zhang X. Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model. J Gene Med. 2007;9:161–9.

    Article  CAS  PubMed  Google Scholar 

  54. Endo T, Toda M, Watanabe M, Iizuka Y, Kubota T, Kitajima M, et al. In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer. Cancer Gene Ther. 2002;9:142–8.

    Article  CAS  PubMed  Google Scholar 

  55. Toda M, Rabkin SD, Kojima H, Martuza RL. Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum Gene Ther. 1999;10:385–93.

    Article  CAS  PubMed  Google Scholar 

  56. Toda M, Iizuka Y, Kawase T, Uyemura K, Kawakami Y. Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV. Cancer Gene Ther. 2002;9:356–64.

    Article  CAS  PubMed  Google Scholar 

  57. Hu JC, Coffin RS, Davis CJ, et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006;12:6737–47.

    Article  CAS  PubMed  Google Scholar 

  58. Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16(15):4005.

    Article  CAS  PubMed  Google Scholar 

  59. Prestwich RJ, Ilett EJ, Errington F, et al. Immune-mediated antitumor activity of reovirus is required for therapy and is independent of direct viral oncolysis and replication. Clin Cancer Res. 2009;15:4374–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. White CL, Twigger KR, Vidal L, et al. Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial. Gene Ther. 2008;15:911–20.

    Article  CAS  PubMed  Google Scholar 

  61. Prestwich RJ, Errington F, Steele LP, et al. Reciprocal human dendritic cell-natural killer cell interactions induce antitumor activity following tumor cell infection by oncolytic reovirus. J Immunol. 2009;183:4312–21.

    Article  CAS  PubMed  Google Scholar 

  62. Gauvrit A, Brandler S, Sapede-Peroz C, et al. Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response. Cancer Res. 2008;68:4882–92.

    Article  CAS  PubMed  Google Scholar 

  63. Li H, Peng KW, Dingli D, et al. Oncolytic measles viruses encoding interferon beta and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy. Cancer Gene Ther. 2010;17(8):550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Heinzerling L, Künzi V, Oberholzer PA, et al. Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. Blood. 2005;106:2287–94.

    Article  CAS  PubMed  Google Scholar 

  65. Gürlevik E, Woller N, Strüver N, et al. Selectivity of oncolytic viral replication prevents antiviral immune response and toxicity, but does not improve antitumoral immunity. Mol Ther. 2010;18:1972–82.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Bristol JA, Zhu M, Ji H, et al. In vitro and in vivo activities of an oncolytic adenoviral vector designed to express GM-CSF. Mol Ther. 2003;7:755–64.

    Article  CAS  PubMed  Google Scholar 

  67. Cerullo V, Pesonen S, Diaconu I, et al. Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients. Cancer Res. 2010;70:4297–309.

    Article  CAS  PubMed  Google Scholar 

  68. Mastrangelo MJ, Maguire HC Jr, Eisenlohr LC, et al. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 1999;6:409–22.

    Article  CAS  PubMed  Google Scholar 

  69. Chuang CM, Monie A, Wu A, et al. Combination of viral oncolysis and tumor-specific immunity to control established tumors. Clin Cancer Res. 2009;15:4581–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zhang YQ, Tsai YC, Monie A, et al. Enhancing the therapeutic effect against ovarian cancer through a combination of viral oncolysis and antigen-specific immunotherapy. Mol Ther. 2010;18:692–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Diaz RM, Galivo F, Kottke T, et al. Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer Res. 2007;67:2840–8.

    Article  CAS  PubMed  Google Scholar 

  72. Wongthida P, Diaz RM, Galivo F, et al. Type III IFN interleukin-28 mediates the antitumor efficacy of oncolytic virus VSV in immune-competent mouse models of cancer. Cancer Res. 2010;70:4539–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Galivo F, Diaz RM, Thanarajasingam U, et al. Interference of CD40L-mediated tumor immunotherapy by oncolytic vesicular stomatitis virus. Hum Gene Ther. 2010;21:439–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Willmon CL, Saloura V, Fridlender ZG, et al. Expression of IFN-beta enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma. Cancer Res. 2009;69:7713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bridle BW, Hanson S, Lichty BD. Combining oncolytic virotherapy and tumor vaccination. Cytokine Growth Factor Rev. 2010;21:143–8.

    Article  CAS  PubMed  Google Scholar 

  76. Qiao J, Kottke T, Willmon C, et al. Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nat Med. 2008;14:37–44.

    Article  CAS  PubMed  Google Scholar 

  77. Vigil A, Martinez O, Chua MA, García-Sastre A. Recombinant Newcastle disease virus as a vaccine vector for cancer therapy. Mol Ther. 2008;16:1883–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. de Gruijl TD, Janssen AB, van Beusechem VW. Arming oncolytic viruses to leverage antitumor immunity. Expert Opin Biol Ther. 2015;15(7):959–71.

    Article  PubMed  Google Scholar 

  79. Breitbach CJ, Paterson JM, Lemay CG, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther. 2007;15(9):1686–93.

    Article  CAS  PubMed  Google Scholar 

  80. Breitbach CJ, Arulanandam R, De Silva N, et al. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013;73(4):1265–75.

    Article  CAS  PubMed  Google Scholar 

  81. Hou W, Chen H, Rojas J, et al. Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. Int J Cancer. 2014;135(5):1238–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Choi IK, Shin H, Oh E, et al. Potent and long-term antiangiogenic efficacy mediated by FP3-expressing oncolytic adenovirus. Int J Cancer. 2015;137(9):2253–69.

    Article  CAS  PubMed  Google Scholar 

  83. McKee TD, Grandi P, Mok W, et al. Degradation of fibrillary collagen in a human melanoma xenograft improves the efficiency of an oncolytic herpes simplex virus vector. Cancer Res. 2006;66(5):2509–13.

    Article  CAS  PubMed  Google Scholar 

  84. Mok W, Boucher Y, Rk J. Matrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus. Cancer Res. 2007;67(22):10664–8.

    Article  CAS  PubMed  Google Scholar 

  85. Guedan S, Rojas JJ, Gros A, et al. Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth. Mol Ther. 2010;18(7):1275–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kim JH, Lee YS, Kim H, et al. Relaxin expression from tumor-targeting adenoviruses and its intratumoral spread, apoptosis induction, and efficacy. J Natl Cancer Inst. 2006;98(20):1482–93.

    Article  CAS  PubMed  Google Scholar 

  87. Montel V, Kleeman J, Agarwal D, et al. Altered metastatic behavior of human breast cancer cells after experimental manipulation of matrix metalloproteinase 8 gene expression. Cancer Res. 2004;64(5):1687–94.

    Article  CAS  PubMed  Google Scholar 

  88. Ilkow CS, Marguerie M, Batenchuk C, et al. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med. 2015;21(5):530–6.

    Article  CAS  PubMed  Google Scholar 

  89. Kirn DH, Wang Y, Liang W, et al. Enhancing poxvirus oncolytic effects through increased spread and immune evasion. Cancer Res. 2008;68:2071–5.

    Article  CAS  PubMed  Google Scholar 

  90. Sampath P, Li J, Hou W, et al. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects. Mol Ther. 2013;21(3):620–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sara E. Berkey .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Berkey, S.E., Thorne, S.H., Bartlett, D.L. (2017). Oncolytic Virotherapy and the Tumor Microenvironment. In: Kalinski, P. (eds) Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy. Advances in Experimental Medicine and Biology, vol 1036. Springer, Cham. https://doi.org/10.1007/978-3-319-67577-0_11

Download citation

Publish with us

Policies and ethics