Intravenous injection of oncolytic virus M1 awakes antitumor T cells and overcomes resistance to checkpoint blockade
Gene set enrichment analysis (GSEA) revealed that upon M1 treatment, apoptotic and inflammation associated genes were largely upregulated, suggesting that M1 killed tumor cells and triggered inflammatory response. The GSEA also revealed that DNA repair pathway was down-regulated in M1 treated tumors, which is consistent with our previous finding that M1 induces DNA damage and then leads to tumor cells apoptosis. Additionally, gene sets marked the release of immune-boosting cytokines such as interferon (IFN)-a, IFN-?and tumor necrosis factor (TNF)-a were deployed in M1 treated tumors, providing potential pro-inflammatory signals to generate antitumor immunity. All the results above demonstrate that M1 induces ICD and shapes TME to an inflammatory state. Overall design: C57BL/6J mice were implanted subcutaneously in the right flank with B16F10 cells at day 0 and treated intravenously with PBS (n=4) or C6V1(M1) (n=4) (1x107 pfu) daily on day 6-10. Tumors were harvested on day 12, total RNA was extracted and then performed RNA-sequencing.