Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cutting both ways: the innate immune response to oncolytic virotherapy

Cancer Gene Therapy volume 29, pages 629–646 (2022)Cite this article

Subjects

Abstract

Oncolytic viruses (OVs), above and beyond infecting and lysing malignant cells, interact with the immune system in complex ways that have important therapeutic significance. While investigation into these interactions is still in its early stages, important insights have been made over the past two decades that will help improve the clinical efficacy of OV-based management strategies in cancer care moving forward. The inherent immunosuppression that defines the tumor microenvironment can be modified by OV infection, and the subsequent recruitment and activation of innate immune cells, in particular, is central to this. Indeed, neutrophils, macrophages, natural killer cells, and dendritic cells, as well as other populations such as myeloid-derived suppressor cells, are key to the immune escape that allows tumors to survive, but their natural response to infection can be exploited by virotherapy. While stimulation of innate immune cells by OVs can initiate antitumor responses, related antiviral activity can limit virus spread and direct cytopathogenic effects. In this review, we highlight how each innate immune cell population influences this balance of antitumor and antiviral forces during virotherapy, some of the important molecular pathways that have been identified, and specific therapeutic targets that have emerged through this work. We discuss the importance of OV-based combination therapies in optimizing antiviral and antitumor innate immune responses stimulated by virotherapy toward tumor eradication, and how these processes vary depending on the tumor and OV in question. Rather than concentrating on a particular OV species in the review, we present the range of effects that have been documented across OV types to emphasize the context-specific nature of these interactions and how this is important in the design of future OV-based treatment approaches.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Innate immune activity within the TME following OV infection and spread.

Similar content being viewed by others

References

  1. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.

    Article  CAS  PubMed  Google Scholar 

  2. Gujar SA, Marcato P, Pan D, Lee PW. Reovirus virotherapy overrides tumor antigen presentation evasion and promotes protective antitumor immunity. Mol Cancer Ther. 2010;9:2924–33.

    Article  CAS  PubMed  Google Scholar 

  3. Lichty BD, Breitbach CJ, Stojdl DF, Bell JC. Going viral with cancer immunotherapy. Nat Rev Cancer. 2014;14:559–67.

    Article  CAS  PubMed  Google Scholar 

  4. Jennings VA, Scott GB, Rose AMS, Scott KJ, Migneco G, Keller B, et al. Potentiating oncolytic virus-induced immune-mediated tumor cell killing using histone deacetylase inhibition. Mol Ther. 2019;27:1139–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bourgeois-Daigneault MC, Roy DG, Falls T, Twumasi-Boateng K, St-Germain LE, Marguerie M, et al. Oncolytic vesicular stomatitis virus expressing interferon-gamma has enhanced therapeutic activity. Mol Ther Oncolytics. 2016;3:16001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lee TJ, Nair M, Banasavadi-Siddegowda Y, Liu J, Nallanagulagari T, Jaime-Ramirez AC, et al. Enhancing therapeutic efficacy of oncolytic herpes simplex virus-1 with integrin beta1 blocking antibody OS2966. Mol Cancer Ther. 2019;18:1127–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bollino D, Colunga A, Li B, Aurelian L. DeltaPK oncolytic activity includes modulation of the tumour cell milieu. J Gen Virol. 2016;97:496–508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nguyen TL, Abdelbary H, Arguello M, Breitbach C, Leveille S, Diallo JS, et al. Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. Proc Natl Acad Sci USA. 2008;105:14981–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu L, Huang TG, Meseck M, Altomonte J, Ebert O, Shinozaki K, et al. rVSV(M Delta 51)-M3 is an effective and safe oncolytic virus for cancer therapy. Hum Gene Ther. 2008;19:635–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fulci G, Dmitrieva N, Gianni D, Fontana EJ, Pan X, Lu Y, et al. Depletion of peripheral macrophages and brain microglia increases brain tumor titers of oncolytic viruses. Cancer Res. 2007;67:9398–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Guo ZS, Parimi V, O’Malley ME, Thirunavukarasu P, Sathaiah M, Austin F, et al. The combination of immunosuppression and carrier cells significantly enhances the efficacy of oncolytic poxvirus in the pre-immunized host. Gene Ther. 2010;17:1465–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lun XQ, Jang JH, Tang N, Deng H, Head R, Bell JC, et al. Efficacy of systemically administered oncolytic vaccinia virotherapy for malignant gliomas is enhanced by combination therapy with rapamycin or cyclophosphamide. Clin Cancer Res. 2009;15:2777–88.

    Article  CAS  PubMed  Google Scholar 

  13. Larsen SK, Gao Y, Basse PH. NK cells in the tumor microenvironment. Crit Rev Oncog. 2014;19:91–105.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hou W, Sampath P, Rojas JJ, Thorne SH. Oncolytic virus-mediated targeting of PGE2 in the tumor alters the immune status and sensitizes established and resistant tumors to immunotherapy. Cancer Cell. 2016;30:108–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dey A, Zhang Y, Castleton AZ, Bailey K, Beaton B, Patel B, et al. The role of neutrophils in measles virus-mediated oncolysis differs between B-cell malignancies and is not always enhanced by GCSF. Mol Ther. 2016;24:184–92.

    Article  CAS  PubMed  Google Scholar 

  16. Francis L, Guo ZS, Liu Z, Ravindranathan R, Urban JA, Sathaiah M, et al. Modulation of chemokines in the tumor microenvironment enhances oncolytic virotherapy for colorectal cancer. Oncotarget 2016;7:22174–85.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Breitbach CJ, De Silva NS, Falls TJ, Aladl U, Evgin L, Paterson J, et al. Targeting tumor vasculature with an oncolytic virus. Mol Ther 2011;19:886–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu Y, Cai J, Liu W, Lin Y, Guo L, Liu X, et al. Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade. Cell Death & Dis. 2020;11:1–13.

    Article  CAS  Google Scholar 

  19. Fu X, Tao L, Rivera A, Xu H, Zhang X. Virotherapy induces massive infiltration of neutrophils in a subset of tumors defined by a strong endogenous interferon response activity. Cancer Gene Ther. 2011;18:785–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Delwar ZM, Kuo Y, Wen YH, Rennie PS, Jia W. Oncolytic virotherapy blockade by microglia and macrophages requires STAT1/3. Cancer Res. 2018;78:718–30.

    Article  CAS  PubMed  Google Scholar 

  21. Denton NL, Chen CY, Hutzen B, Currier MA, Scott T, Nartker B, et al. Myelolytic treatments enhance oncolytic herpes virotherapy in models of Ewing sarcoma by modulating the immune microenvironment. Mol Ther Oncolytics. 2018;11:62–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Raff M, Alberts B, Lewis J, Johnson A, Roberts K. Molecular biology of the cell. 4th edn. National Center for Biotechnology InformationÕs Bookshelf; New York: Garland Science; 2002.

  23. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. McDonald DR, Levy O. 3 - Innate immunity. In: Rich RR, Fleisher TA, Shearer WT, Schroeder HW, Frew AJ, Weyand CM, editors. Clinical immunology. 5th ed. London: Content Repository Only!; 2019. p. 39-53.e1.

  25. Mejías-Pérez E, Carreño-Fuentes L, Esteban M. Development of a safe and effective vaccinia virus oncolytic vector WR-Δ4 with a set of gene deletions on several viral pathways. Mol Ther - Oncolytics. 2018;8:27–40.

    Article  PubMed  CAS  Google Scholar 

  26. Sionov RV, Fridlender ZG, Granot Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 2015;8:125–58.

    Article  CAS  PubMed  Google Scholar 

  27. Hagerling C, Werb Z. Neutrophils: critical components in experimental animal models of cancer. Semin Immunol. 2016;28:197–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Andzinski L, Kasnitz N, Stahnke S, Wu CF, Gereke M, von Kockritz-Blickwede M, et al. Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human. Int J Cancer. 2016;138:1982–93.

    Article  CAS  PubMed  Google Scholar 

  29. Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol. 2019;16:601–20.

    Article  PubMed  Google Scholar 

  30. Powell DR, Huttenlocher A. Neutrophils in the tumor microenvironment. Trends Immunol. 2016;37:41–52.

    Article  CAS  PubMed  Google Scholar 

  31. Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33:949–55.

    Article  CAS  PubMed  Google Scholar 

  32. Naumenko V, Turk M, Jenne CN, Kim S-J. Neutrophils in viral infection. Cell Tissue Res. 2018;371:505–16.

    Article  CAS  PubMed  Google Scholar 

  33. Stegelmeier AA, Chan L, Mehrani Y, Petrik JJ, Wootton SK, Bridle B, et al. Characterization of the impact of oncolytic vesicular stomatitis virus on the trafficking, phenotype, and antigen presentation potential of neutrophils and their ability to acquire a non-structural viral protein. Int J Mol Sci. 2020;21:6347.

    Article  CAS  PubMed Central  Google Scholar 

  34. Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, McGuire A, Parato KA, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther. 2007;15:1686–93.

    Article  CAS  PubMed  Google Scholar 

  35. Holl EK, Brown MC, Boczkowski D, McNamara MA, George DJ, Bigner DD, et al. Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models. Oncotarget 2016;7:79828–41.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Yan C, Yang Q, Gong Z. Tumor-associated neutrophils and macrophages promote gender disparity in hepatocellular carcinoma in zebrafish. Cancer Res. 2017;77:1395–407.

    Article  CAS  PubMed  Google Scholar 

  37. Di Pilato M, Mejias-Perez E, Zonca M, Perdiguero B, Gomez CE, Trakala M, et al. NFkappaB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses. Proc Natl Acad Sci USA. 2015;112:E1333–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Zhang Y, Patel B, Dey A, Ghorani E, Rai L, Elham M, et al. Attenuated, oncolytic, but not wild-type measles virus infection has pleiotropic effects on human neutrophil function. J Immunol. 2012;188:1002–10.

    Article  CAS  PubMed  Google Scholar 

  39. Howell MD, Jones JF, Kisich KO, Streib JE, Gallo RL, Leung DYM. Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum. J Immunol. 2004;172:1763–7.

    Article  CAS  PubMed  Google Scholar 

  40. Hayashi K, Hooper LC, Okuno T, Takada Y, Hooks JJ. Inhibition of HSV-1 by chemoattracted neutrophils: supernatants of corneal epithelial cells (HCE) and macrophages (THP-1) treated with virus components chemoattract neutrophils (PMN), and supernatants of PMN treated with these conditioned media inhibit viral growth. Arch Virol. 2012;157:1377–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Taipale K, Liikanen I, Koski A, Heiskanen R, Kanerva A, Hemminki O, et al. Predictive and prognostic clinical variables in cancer patients treated with adenoviral oncolytic immunotherapy. Mol Ther. 2016;24:1323–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Grote D, Cattaneo R, Fielding AK. Neutrophils contribute to the measles virus-induced antitumor effect: enhancement by granulocyte macrophage colony-stimulating factor expression. Cancer Res. 2003;63:6463–8.

    CAS  PubMed  Google Scholar 

  43. Agoulnik I, Gentschev I, Müller M, Adelfinger M, Weibel S, Grummt F, et al. Efficient colonization and therapy of human hepatocellular carcinoma (HCC) using the oncolytic vaccinia virus strain GLV-1h68. PLoS ONE. 2011;6:e22069.

    Article  CAS  Google Scholar 

  44. Lesniak MS, Moralès O, Richard A, Martin N, Mrizak D, Sénéchal M, et al. Activation of a helper and not regulatory human CD4+ T cell response by oncolytic H-1 parvovirus. PLoS ONE. 2012;7:e32197.

    Article  CAS  Google Scholar 

  45. Peng KW, Frenzke M, Myers R, Soeffker D, Harvey M, Greiner S, et al. Biodistribution of oncolytic measles virus after intraperitoneal administration into Ifnar-CD46Ge transgenic mice. Hum Gene Ther. 2003;14:1565–77.

    Article  CAS  PubMed  Google Scholar 

  46. Wongthida P, Diaz RM, Galivo F, Kottke T, Thompson J, Melcher A, et al. VSV oncolytic virotherapy in the B16 model depends upon intact MyD88 signaling. Mol Ther. 2011;19:150–8.

    Article  CAS  PubMed  Google Scholar 

  47. Clifford AB, Elnaggar AM, Robison RA, O’Neill K. Investigating the role of macrophages in tumor formation using a MaFIA mouse model. Oncol Rep. 2013;30:890–6.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang L, Wang W, Wang R, Zhang N, Shang H, Bi Y, et al. Reshaping the immune microenvironment by oncolytic herpes simplex virus in murine pancreatic ductal adenocarcinoma. Mol Ther. 2020;29:744–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Gujar SA, Lee PW. Oncolytic virus-mediated reversal of impaired tumor antigen presentation. Front Oncol. 2014;4:77.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Jakeman PG, Hills TE, Fisher KD, Seymour LW. Macrophages and their interactions with oncolytic viruses. Curr Opin Pharm. 2015;24:23–9.

    Article  CAS  Google Scholar 

  51. Ostuni R, Kratochvill F, Murray PJ, Natoli G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 2015;36:229–39.

    Article  CAS  PubMed  Google Scholar 

  52. Clements DR, Murphy JP, Sterea A, Kennedy BE, Kim Y, Helson E, et al. Quantitative temporal in vivo proteomics deciphers the transition of virus-driven myeloid cells into M2 macrophages. J Proteome Res. 2017;16:3391–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ottolino-Perry K, Acuna SA, Angarita FA, Sellers C, Zerhouni S, Tang N, et al. Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer. Mol Oncol. 2015;9:1539–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Masemann D, Köther K, Kuhlencord M, Varga G, Roth J, Lichty BD, et al. Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages. OncoImmunology. 2018;7:e1423171.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Liu S, Zhang J, Fang S, Zhang Q, Zhu G, Tian Y, et al. Macrophage polarization contributes to the efficacy of an oncolytic HSV-1 targeting human uveal melanoma in a murine xenograft model. Exp Eye Res. 2021;202:108285.

    Article  CAS  PubMed  Google Scholar 

  56. Liu YP, Suksanpaisan L, Steele MB, Russell SJ, Peng KW. Induction of antiviral genes by the tumor microenvironment confers resistance to virotherapy. Sci Rep. 2013;3:2375.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Denton NL, Chen CY, Scott TR, Cripe TP. Tumor-associated macrophages in oncolytic virotherapy: friend or foe?. Biomedicines. 2016;4:13.

    Article  PubMed Central  CAS  Google Scholar 

  58. Wiegertjes GF, Wentzel AS, Spaink HP, Elks PM, Fink IR. Polarization of immune responses in fish: the ‘macrophages first’ point of view. Mol Immunol. 2016;69:146–56.

    Article  CAS  PubMed  Google Scholar 

  59. Saha D, Martuza RL, Rabkin SD. Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade. Cancer Cell. 2017;32:253–67. e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kleijn A, Kloezeman J, Treffers-Westerlaken E, Fulci G, Leenstra S, Dirven C, et al. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity. PLoS ONE. 2014;9:e97495.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Tan DQ, Zhang L, Ohba K, Ye M, Ichiyama K, Yamamoto N. Macrophage response to oncolytic paramyxoviruses potentiates virus-mediated tumor cell killing. Eur J Immunol. 2016;46:919–28.

    Article  CAS  PubMed  Google Scholar 

  62. Jiang H, Clise-Dwyer K, Ruisaard KE, Fan X, Tian W, Gumin J, et al. Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model. PLoS ONE. 2014;9:e97407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Milenova IE, Ven RVD, Dong W, Beusechem VWV, Gruijl TDD. Abstract 4133: The in vitro melanoma tumor microenvironment conditions macrophages to an immunosuppressive M2-like phenotype, which is reversible by oncolytic virus ORCA-010 with immune modulators. Cancer Res. 2019;79:4133.

    Article  Google Scholar 

  64. Alvarez-Breckenridge CA, Yu J, Price R, Wojton J, Pradarelli J, Mao H, et al. NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med. 2012;18:1827–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Alkayyal AA, Tai LH, Kennedy MA, de Souza CT, Zhang J, Lefebvre C, et al. NK-cell recruitment is necessary for eradication of peritoneal carcinomatosis with an IL12-expressing maraba virus cellular vaccine. Cancer Immunol Res. 2017;5:211–21.

    Article  CAS  PubMed  Google Scholar 

  66. Annels NE, Simpson GR, Denyer M, Arif M, Coffey M, Melcher A, et al. Oncolytic reovirus-mediated recruitment of early innate immune response reverses immunotherapy-resistance in prostate tumours by inducing a T-cell inflamed microenvironment. Mol Ther– Oncolytics. 2020;20:434–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Medina-Echeverz J, Hinterberger M, Testori M, Geiger M, Giessel R, Bathke B, et al. Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies. Nat Commun. 2019;10:5041.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  69. Kim Y, Yoo JY, Lee TJ, Liu J, Yu J, Caligiuri MA, et al. Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy. Proc Natl Acad Sci USA. 2018;115:4927–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yoo JY, Jaime-Ramirez AC, Bolyard C, Dai H, Nallanagulagari T, Wojton J, et al. Bortezomib treatment sensitizes oncolytic HSV-1-treated tumors to NK cell immunotherapy. Clin Cancer Res. 2016;22:5265–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. van Vloten JP, Workenhe ST, Wootton SK, Mossman KL, Bridle BW. Critical interactions between immunogenic cancer cell death, oncolytic viruses, and the immune system define the rational design of combination immunotherapies. J Immunol. 2018;200:450–8.

    Article  PubMed  CAS  Google Scholar 

  72. López González M, Ven R, Haan H, Eck van der Sluijs J, Dong W, Beusechem VW, et al. Oncolytic adenovirus ORCA‐010 increases the type 1 T cell stimulatory capacity of melanoma‐conditioned dendritic cells. Clin Exp Immunol. 2020;201:145–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Ma J, Ramachandran M, Jin C, Quijano-Rubio C, Martikainen M, Yu D, et al. Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer. Cell Death Dis. 2020;11:1–15.

    Article  CAS  Google Scholar 

  74. Xu Q, Rangaswamy US, Wang W, Robbins SH, Harper J, Jin H, et al. Evaluation of Newcastle disease virus mediated dendritic cell activation and cross‐priming tumor‐specific immune responses ex vivo. Int J Cancer. 2019;146:531–41.

    Article  PubMed  CAS  Google Scholar 

  75. Zafar S, Basnet S, Launonen I-M, Quixabeira DCA, Santos J, Hemminki O, et al. Oncolytic adenovirus type 3 coding for CD40L facilitates dendritic cell therapy of prostate cancer in humanized mice and patient samples. Hum Gene Ther. 2020;32:192–202.

    Article  CAS  Google Scholar 

  76. Diallo JS, Le Boeuf F, Lai F, Cox J, Vaha-Koskela M, Abdelbary H, et al. A high-throughput pharmacoviral approach identifies novel oncolytic virus sensitizers. Mol Ther. 2010;18:1123–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Evgin L, Acuna SA, Tanese de Souza C, Marguerie M, Lemay CG, Ilkow CS, et al. Complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques. Mol Ther. 2015;23:1066–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wakimoto H, Ikeda K, Abe T, Ichikawa T, Hochberg FH, Ezekowitz RAB, et al. The complement response against an oncolytic virus is species-specific in its activation pathways. Mol Ther. 2002;5:275–82.

    Article  CAS  PubMed  Google Scholar 

  79. Kim MK, Breitbach CJ, Moon A, Heo J, Lee YK, Cho M, et al. Oncolytic and immunotherapeutic vaccinia induces antibody-mediated complement-dependent cancer cell lysis in humans. Sci Transl Med. 2013;5:185ra63.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Toronto, Toronto, ON, Canada

    David Mealiea & J. Andrea McCart

  2. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    David Mealiea & J. Andrea McCart

Authors
  1. David Mealiea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Andrea McCart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Mealiea.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mealiea, D., McCart, J.A. Cutting both ways: the innate immune response to oncolytic virotherapy. Cancer Gene Ther 29, 629–646 (2022). https://doi.org/10.1038/s41417-021-00351-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-021-00351-3

This article is cited by

Search

Advanced search

Quick links