Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Apr:51:83-90.
doi: 10.1016/j.coi.2018.03.008. Epub 2018 Mar 16.

Oncolytic viruses and immunity

Shyambabu Chaurasiya  1 , Nanhai G Chen  2 , Yuman Fong  3
Affiliations
Review

Oncolytic viruses and immunity

Shyambabu Chaurasiya et al. Curr Opin Immunol. 2018 Apr.

Abstract

Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy. In this review we discuss the importance of the involvement of innate and adaptive immunity for therapeutic efficacy of OVs, and the rational combination of OVs with other immunotherapies for further enhancement of overall therapeutic outcome.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Modulation of the tumor microenvironment by OVs and elicitation of anti-tumor immunity.
(i) OVs convert immunologically “COLD” tumors to immunologically “HOT” tumors: tumors generally have high concentration of immunesuppressive cells and cytokines, which make them immunologically less responsive i.e. immunologically “COLD”. OVs induce inflammation and inhibit immunosuppressive cells (Tregs and MDSCs) and cytokines (IL-10 and TGF-β). Conversely, OVs also increase proinflammatory cytokines (IL-6 and IL-8) and foster tumor infiltration by NK cells and other TILs. This complex modulation of the TME by OVs converts the tumor to inflamed, immunologically “HOT”. (ii) OV infection increases NK cell-mediated killing of tumor cells: tumor cells tend to reduce their MHC I levels in response to virus infection. Reduction in MHC I allows recognition and killing of virus infected cancer cells by NK cells. (iii) Oncolysis by OVs causes the release of tumor-associated/specific antigens, and OVs also induce immunogenic cell death (ICD). (iv) Antigen-loaded APCs migrate to the lymph node, where (v) they cross-present tumor antigens to CD8+ T cells. (vi) Following activation, the tumor-specific CD8+ T cells undergo expansion. (vii) Finally, the tumor-specific T cells move to both OV injected and uninjected tumors (distant metastases) where they can exert anti-tumor effect.
See this image and copyright information in PMC

References

    1. Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646–674. - PubMed
    1. Hashiro G, Loh PC, Yau JT: The preferential cytotoxicity of reovirus for certain transformed cell lines. Arch Virol 1977, 54:307–315. - PubMed
    1. Coffey MC, Strong JE, Forsyth PA, Lee PW: Reovirus therapy of tumors with activated Ras pathway. Science 1998, 282:1332–1334. - PubMed
    1. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC: Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 2000, 6:821–825. - PubMed
    1. Heise C, Hermiston T, Johnson L, Brooks G, Sampson-Johannes A, Williams A, Hawkins L, Kirn D: An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 2000, 6:1134–1139. - PubMed

Publication types