Skip to main content
SpringerLink
Log in

Cancer Immunology

  • Chapter
  • First Online:
Comprehensive Clinical Plasma Medicine

  • 1294 Accesses

Abstract

Cold physical plasma is receiving increasing attention in oncology. Generation of a plethora of different reactive species is a major trait of cold plasmas. Reactive species and mitochondria have been the focus of cancer and cell death research for many decades. This links the field of plasma medicine to past and ongoing work in oncology. In the two extremes, cell death can be of tolerogenic or immunogenic nature. The latter is capable of inducing an immune response (immunogenic cell death, ICD). ICD is associated with tumor-reactive T cells, which are positively linked to survival in cancer patients. Several physical treatment modalities were shown to be potent ICD inducers, for example, ionizing radiation, and hyperthermia. Recent reports suggest that cold plasma may also increase the immunogenicity of cancer cells. This book chapter describes current concepts of immunity in oncology, sheds light on physical therapies in ICD, outlines current research in plasma-induced immunogenic cell death (PICD), and provides an outlook on future research and directions necessary to provide potential therapeutic benefit of plasma treatment in oncology.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kramer A, Bekeschus S, Broker BM, Schleibinger H, Razavi B, Assadian O. Maintaining health by balancing microbial exposure and prevention of infection: the hygiene hypothesis versus the hypothesis of early immune challenge. J Hosp Infect. 2013;83(Suppl 1):S29–34.

    Article  Google Scholar 

  2. Leliefeld PH, Wessels CM, Leenen LP, Koenderman L, Pillay J. The role of neutrophils in immune dysfunction during severe inflammation. Crit Care. 2016;20(1):73.

    Article  Google Scholar 

  3. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat Rev Immunol. 2006;6(10):715–27.

    Article  CAS  Google Scholar 

  4. Penn I, Starzl TE. Malignant tumors arising de novo in immunosuppressed organ transplant recipients. Transplantation. 1972;14(4):407–17.

    Article  CAS  Google Scholar 

  5. Raulet DH, Guerra N. Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol. 2009;9(8):568–80.

    Article  CAS  Google Scholar 

  6. Abdollahi A, Folkman J. Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resist Updat. 2010;13(1–2):16–28.

    Article  CAS  Google Scholar 

  7. Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara HM, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Choi BK, Kwon BS. Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015;35(Suppl):S185–98.

    Article  Google Scholar 

  8. Ehlers G, Fridman M. Abscopal effect of radiation in papillary adenocarcinoma. Br J Radiol. 1973;46(543):220–2.

    Article  CAS  Google Scholar 

  9. Mole RH. Whole body irradiation; radiobiology or medicine? Br J Radiol. 1953;26(305):234–41.

    Article  CAS  Google Scholar 

  10. Schirrmacher V. Cancer-reactive memory t cells from bone marrow: spontaneous induction and therapeutic potential (review). Int J Oncol. 2015;47(6):2005–16.

    Article  CAS  Google Scholar 

  11. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.

    Article  CAS  Google Scholar 

  12. Claude L, Perol D, Ray-Coquard I, Petit T, Blay JY, Carrie C, Bachelot T. Lymphopenia: a new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma. Radiother Oncol. 2005;76(3):334–9.

    Article  Google Scholar 

  13. Galon J, Franchimont D, Hiroi N, Frey G, Boettner A, Ehrhart-Bornstein M, O’Shea JJ, Chrousos GP, Bornstein SR. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J. 2002;16(1):61–71.

    Article  CAS  Google Scholar 

  14. Panici PB, Maggioni A, Hacker N, Landoni F, Ackermann S, Campagnutta E, Tamussino K, Winter R, Pellegrino A, Greggi S, Angioli R, Manci N, Scambia G, Dell’Anna T, Fossati R, Floriani I, Rossi RS, Grassi R, Favalli G, Raspagliesi F, Giannarelli D, Martella L, Mangioni C. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst. 2005;97(8):560–6.

    Article  Google Scholar 

  15. Weiner HL, Cohen JA. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult Scler. 2002;8(2):142–54.

    Article  CAS  Google Scholar 

  16. Fraser JM, Janicki CN, Raveney BJ, Morgan DJ. Abortive activation precedes functional deletion of cd8+ t cells following encounter with self-antigens expressed by resting b cells in vivo. Immunology. 2006;119(1):126–33.

    Article  CAS  Google Scholar 

  17. Wyllie AH. Cell death: a new classification separating apoptosis from necrosis. In: Bowen ID, Lockshin RA, editors. Cell death in biology and pathology. Dordrecht: Springer; 1981. p. 9–34.

    Chapter  Google Scholar 

  18. Green DR, Ferguson T, Zitvogel L, Kroemer G. Immunogenic and tolerogenic cell death. Nat Rev Immunol. 2009;9(5):353–63.

    Article  CAS  Google Scholar 

  19. Garg AD, Romano E, Rufo N, Agostinis P. Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation. Cell Death Differ. 2016;23(6):938–51.

    Article  CAS  Google Scholar 

  20. Garg AD, Dudek AM, Agostinis P. Cancer immunogenicity, danger signals, and damps: what, when, and how? Biofactors. 2013;39(4):355–67.

    Article  CAS  Google Scholar 

  21. Fehres CM, Unger WW, Garcia-Vallejo JJ, van Kooyk Y. Understanding the biology of antigen cross-presentation for the design of vaccines against cancer. Front Immunol. 2014;5:149.

    Article  Google Scholar 

  22. Garg AD, Martin S, Golab J, Agostinis P. Danger signalling during cancer cell death: origins, plasticity and regulation. Cell Death Differ. 2014;21(1):26–38.

    Article  CAS  Google Scholar 

  23. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.

    Article  CAS  Google Scholar 

  24. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13(1):54–61.

    Article  CAS  Google Scholar 

  25. Adkins I, Fucikova J, Garg AD, Agostinis P, Spisek R. Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy. Oncoimmunology. 2014;3(12):e968434.

    Article  Google Scholar 

  26. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97–111.

    Article  CAS  Google Scholar 

  27. Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015;41(6):503–10.

    Article  Google Scholar 

  28. Golden EB, Apetoh L. Radiotherapy and immunogenic cell death. Semin Radiat Oncol. 2015;25(1):11–7.

    Article  Google Scholar 

  29. Kamensek U, Kos S, Sersa G. Adjuvant immunotherapy as a tool to boost effectiveness of electrochemotherapy. Handbook of electroporation. 2016. p. 1–16.

    Google Scholar 

  30. Mir LM, Gehl J, Sersa G, Collins CG, Garbay JR, Billard V, Geertsen PF, Rudolf Z, O'Sullivan GC, Marty M. Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the cliniporator (tm) by means of invasive or non-invasive electrodes. EJC Suppl. 2006;4(11):14–25.

    Article  CAS  Google Scholar 

  31. Matthiessen LW, Johannesen HH, Hendel HW, Moss T, Kamby C, Gehl J. Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase ii clinical trial. Acta Oncol. 2012;51(6):713–21.

    Article  Google Scholar 

  32. Snoj M, Matthiessen LW. Electrochemotherapy of cutaneous metastases. Handbook of electroporation. 2016. p. 1–14.

    Google Scholar 

  33. Griffin LL, Lear JT. Photodynamic therapy and non-melanoma skin cancer. Cancers (Basel). 2016;8(10).

    Article  Google Scholar 

  34. DeRosa MC, Crutchley RJ. Photosensitized singlet oxygen and its applications. Coord Chem Rev. 2002;233:351–71.

    Article  Google Scholar 

  35. Mallidi S, Anbil S, Bulin AL, Obaid G, Ichikawa M, Hasan T. Beyond the barriers of light penetration: strategies, perspectives and possibilities for photodynamic therapy. Theranostics. 2016;6(13):2458–87.

    Article  CAS  Google Scholar 

  36. Duan X, Chan C, Guo N, Han W, Weichselbaum RR, Lin W. Photodynamic therapy mediated by nontoxic core-shell nanoparticles synergizes with immune checkpoint blockade to elicit antitumor immunity and antimetastatic effect on breast cancer. J Am Chem Soc. 2016;138(51):16686–95.

    Article  CAS  Google Scholar 

  37. Maeding N, Verwanger T, Krammer B. Boosting tumor-specific immunity using pdt. Cancers (Basel). 2016;8(10)

    Article  Google Scholar 

  38. Tanaka M, Kataoka H, Yano S, Sawada T, Akashi H, Inoue M, Suzuki S, Inagaki Y, Hayashi N, Nishie H, Shimura T, Mizoshita T, Mori Y, Kubota E, Tanida S, Takahashi S, Joh T. Immunogenic cell death due to a new photodynamic therapy (pdt) with glycoconjugated chlorin (g-chlorin). Oncotarget. 2016;7(30):47242–51.

    Article  Google Scholar 

  39. Frey B, Weiss EM, Rubner Y, Wunderlich R, Ott OJ, Sauer R, Fietkau R, Gaipl US. Old and new facts about hyperthermia-induced modulations of the immune system. Int J Hyperthermia. 2012;28(6):528–42.

    Article  CAS  Google Scholar 

  40. Larson N, Gormley A, Frazier N, Ghandehari H. Synergistic enhancement of cancer therapy using a combination of heat shock protein targeted hpma copolymer-drug conjugates and gold nanorod induced hyperthermia. J Control Release. 2013;170(1):41–50.

    Article  CAS  Google Scholar 

  41. Fucikova J, Moserova I, Truxova I, Hermanova I, Vancurova I, Partlova S, Fialova A, Sojka L, Cartron PF, Houska M, Rob L, Bartunkova J, Spisek R. High hydrostatic pressure induces immunogenic cell death in human tumor cells. Int J Cancer. 2014;135(5):1165–77.

    Article  CAS  Google Scholar 

  42. Moserova I, Truxova I, Garg AD, Tomala J, Agostinis P, Cartron PF, Vosahlikova S, Kovar M, Spisek R, Fucikova J. Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death. Oncoimmunology. 2017;6(1):e1258505.

    Article  Google Scholar 

  43. Vandenberk L, Belmans J, Van Woensel M, Riva M, Van Gool SW. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines. Front Immunol. 2015;6:663.

    PubMed  Google Scholar 

  44. Schmidt-Bleker A, Bansemer R, Reuter S, Weltmann K-D. How to produce an nox- instead of ox-based chemistry with a cold atmospheric plasma jet. Plasma Process Polym. 2016;13(11):1120–7.

    Article  Google Scholar 

  45. Jablonowski H, von Woedtke T. Research on plasma medicine-relevant plasma–liquid interaction: what happened in the past five years? Clin Plasma Med. 2015;3(2):42–52.

    Article  Google Scholar 

  46. Dunnbier M, Schmidt-Bleker A, Winter J, Wolfram M, Hippler R, Weltmann KD, Reuter S. Ambient air particle transport into the effluent of a cold atmospheric-pressure argon plasma jet investigated by molecular beam mass spectrometry. J Phys D. 2013;46(43):435203.

    Article  Google Scholar 

  47. Bekeschus S, Wende K, Hefny MM, Rodder K, Jablonowski H, Schmidt A, Woedtke TV, Weltmann KD, Benedikt J. Oxygen atoms are critical in rendering thp-1 leukaemia cells susceptible to cold physical plasma-induced apoptosis. Sci Rep. 2017;7(1):2791.

    Article  Google Scholar 

  48. Lin A, Truong B, Patel S, Kaushik N, Choi EH, Fridman G, Fridman A, Miller V. Nanosecond-pulsed dbd plasma-generated reactive oxygen species trigger immunogenic cell death in a549 lung carcinoma cells through intracellular oxidative stress. Int J Mol Sci. 2017;18(5)

    Article  Google Scholar 

  49. Bekeschus S, Roder K, Fregin B, Otto O, Lippert M, Weltmann KD, Wende K, Schmidt A, Gandhirajan RK. Toxicity and immunogenicity in murine melanoma following exposure to physical plasma-derived oxidants. Oxidative Med Cell Longev. 2017;2017:4396467.

    Google Scholar 

  50. Lin A, Truong B, Pappas A, Kirifides L, Oubarri A, Chen S, Lin S, Dobrynin D, Fridman G, Fridman A, Sang N, Miller V. Uniform nanosecond pulsed dielectric barrier discharge plasma enhances anti-tumor effects by induction of immunogenic cell death in tumors and stimulation of macrophages. Plasma Process Polym. 2015;12(12):1392–9.

    Article  CAS  Google Scholar 

  51. Kaushik NK, Kaushik N, Min B, Choi KH, Hong YJ, Miller V, Fridman A, Choi EH. Cytotoxic macrophage-released tumour necrosis factor-alpha (tnf-alpha) as a killing mechanism for cancer cell death after cold plasma activation. J Phys D. 2016;49(8):084001.

    Article  Google Scholar 

  52. Kazue M, Kenta Y, Yuki S, Taketoshi A, Ryo O. Anti-tumor immune response induced by nanosecond pulsed streamer discharge in mice. J Phys D. 2017;50(12):12LT01.

    Article  Google Scholar 

  53. Miller V, Lin A, Fridman G, Dobrynin D, Fridman A. Plasma stimulation of migration of macrophages. Plasma Process Polym. 2014;11(12):1193–7.

    Article  CAS  Google Scholar 

  54. Bekeschus S, Winterbourn CC, Kolata J, Masur K, Hasse S, Broker BM, Parker HA. Neutrophil extracellular trap formation is elicited in response to cold physical plasma. J Leukoc Biol. 2016;100(4):791–9.

    Article  CAS  Google Scholar 

  55. Bekeschus S, Kolata J, Muller A, Kramer A, Weltmann K-D, Broker B, Masur K. Differential viability of eight human blood mononuclear cell subpopulations after plasma treatment. Plasma Med. 2013;3(1–2):1–13.

    Article  Google Scholar 

  56. Bundscherer L, Bekeschus S, Tresp H, Hasse S, Reuter S, Weltmann K-D, Lindequist U, Masur K. Viability of human blood leucocytes compared with their respective cell lines after plasma treatment. Plasma Med. 2013;3(1–2):71–80.

    Article  Google Scholar 

  57. Bekeschus S, Iseni S, Reuter S, Masur K, Weltmann K-D. Nitrogen shielding of an argon plasma jet and its effects on human immune cells. IEEE Trans Plasma Sci. 2015;43(3):776–81.

    Article  CAS  Google Scholar 

  58. Bekeschus S, Rödder K, Schmidt A, Stope MB, von Woedtke T, Miller V, Fridman A, Weltmann K-D, Masur K, Metelmann H-R, Wende K, Hasse S. Cold physical plasma selects for specific t helper cell subsets with distinct cells surface markers in a caspase-dependent and nf-κb-independent manner. Plasma Process Polym. 2016;13(12):1144–50.

    Article  CAS  Google Scholar 

  59. Wende K, Reuter S, von Woedtke T, Weltmann KD, Masur K. Redox-based assay for assessment of biological impact of plasma treatment. Plasma Process Polym. 2014;11(7):655–63.

    Article  CAS  Google Scholar 

  60. Miller V, Lin A, Fridman A. Why target immune cells for plasma treatment of cancer. Plasma Chem Plasma Process. 2016;36(1):259–68.

    Article  CAS  Google Scholar 

  61. Garg AD, Vandenberk L, Koks C, Verschuere T, Boon L, Van Gool SW, Agostinis P. Dendritic cell vaccines based on immunogenic cell death elicit danger signals and t cell-driven rejection of high-grade glioma. Sci Transl Med. 2016;8(328):328ra327.

    Article  Google Scholar 

  62. Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M, Gullestad HP, Ryder T, Lislerud K, Hammerstad H, Gaudernack G. Phase i/ii trial of melanoma therapy with dendritic cells transfected with autologous tumor-mrna. Cancer Gene Ther. 2006;13(10):905–18.

    Article  CAS  Google Scholar 

  63. Vandenberk L, Garg AD, Verschuere T, Koks C, Belmans J, Beullens M, Agostinis P, De Vleeschouwer S, Van Gool SW. Irradiation of necrotic cancer cells, employed for pulsing dendritic cells (dcs), potentiates dc vaccine-induced antitumor immunity against high-grade glioma. Oncoimmunology. 2016;5(2):e1083669.

    Article  Google Scholar 

  64. Garg AD, Coulie PG, Van den Eynde BJ, Agostinis P. Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape. Trends Immunol. 2017;38:577–93.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Leibniz-Institute for Plasma Science and Technology, ZIK Plasmatis, Greifswald, Germany

    Sander Bekeschus

  2. GREMI UMR-6606 CNRS, Université d’Orléans, Orleans, France

    Jean-Michel Pouvesle

  3. Nyheim Plasma Institute, Drexel University, Camden, NJ, USA

    Alexander Fridman & Vandana Miller

Authors
  1. Sander Bekeschus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-Michel Pouvesle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Fridman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vandana Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sander Bekeschus .

Editor information

Editors and Affiliations

  1. University Medicine Greifswald, Department of Oral and Maxillofacial Surgery/Plastic Surgery, Greifswald, Germany

    Hans-Robert Metelmann

  2. Leibniz Institute for Plasma Science and Technology (INP Greifswald) and University Medicine Greifswald Institute for Hygiene and Environmental Medicine, Greifswald, Germany

    Thomas von Woedtke

  3. Leibniz Institute for Plasma Science and Technology (INP Greifswald), Greifswald, Germany

    Klaus-Dieter Weltmann

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bekeschus, S., Pouvesle, JM., Fridman, A., Miller, V. (2018). Cancer Immunology. In: Metelmann, HR., von Woedtke, T., Weltmann, KD. (eds) Comprehensive Clinical Plasma Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-67627-2_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-67627-2_24

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-67626-5

  • Online ISBN: 978-3-319-67627-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation