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Inactivated SARS-CoV-2 Reprograms the Tumor Immune Microenvironment and Elicits Anti-Tumor Response in Melanoma and Triple Negative Breast Cancer Murine Model

Eileena F Giurini, Michael Williams, Adam Morin, Andrew Zloza, Kajal H Gupta

Following the breakthrough of Immune Checkpoint Inhibitors (ICIs), a new era of immuno-oncology agents has emerged and established immunotherapy as a part of cancer treatment. Despite the improving outcomes and durability of response to ICIs, unfortunately many patients with initial response are known to develop acquired resistance later. There is increasing interest in potentially using anti-pathogen immune response to induce an antitumor immune response, which has led to rethinking into how the efficacy of anti-pathogen could be further enhanced. The immunostimulatory effects of anti-pathogen treated tumors in combinations with ICI are known to potentially amplify anti-tumor immunity resulting in increased tumor responses and improved outcomes. Antipathogen treated tumors are immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival. Our research group has previously demonstrated that tumors can be converted from “cold” to “hot” by intratumoral injection of a commercially available seasonal influenza vaccine. In continuation with our work, in deciphering the role of anti-viral immunity in tumor immunology, we studied the role of inactivated SARSCoV- 2 virus as anti-tumor. Here we report that intratumoral injections of inactivated SARS-CoV-2 converts the immunologically cold tumors to hot tumors by generating anti-tumor mediated CD8 T cells. Our findings suggest that inactivated SARS-CoV-2 can be used as an immune modulator in immunotherapy in melanoma and triple negative breast cancer.