Cancer immunotherapy using virus-specific memory CD8 T cells for targeting tumor cells with viral infections 2856

Abstract Description Cancer is a global health issue that needs to be solved; therefore, many efforts have been paid to reinvigorate exhausted T cells. Despite these attempts, cancer treatment has not been conquered due to the deficiency of tumor antigens and the expression of immune suppressive molecules. To overcome these problems, we hypothesized that tumor cells infected with viruses are targeted by virus-specific memory CD8 T cells. To test this hypothesis, we administered B16F10 melanoma cells subcutaneously into naïve mice containing LCMV-specific memory P14 cells followed by intratumoral LCMV infections. We confirmed viral infections of tumor cells and found that the frequencies and numbers of P14 cells in the tumors increased in the virus-infected group compared to controls until D10 post infection (pi). The mice with viral infections survived longer than the control mice did, but the tumor growth persisted despite the presence of viral infections. To enhance tumor control, we examined tumor microenvironments and observed that the levels of IL-10 in the infected tumors elevated on D7 and D10 pi compared to control tumors. We then blocked IL-10R with an antibody and found that the tumor growth was delayed compared to control’s, suggesting that IL-10 interrupted anti-tumor immunity. Taken together, we propose a novel strategy that will further expand the variety of cancer therapies by using virus-specific memory CD8 T cells to destroy tumor cells presenting viral antigens. Funding Sources Supported by National Research Foundation of Korea (NRF) -2019R1A6A1A03031807; NRF-2021R1A2C2004279; NRF-00222762 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)