An Irf2-expressing oncolytic virus changes the susceptibility of tumor to antitumor T cells and promotes promotes tumor clearance
According to our previous studies, IRF1-deficient (IRF1-KO) tumor cells showed significantly reduced tumor growth when injected in several syngeneic mouse models including the B16-F10 melanoma, indicating that tumor cells require IRF1 for sustained tumor progression. Depletion of CD8+ T cells or NK cells could restore tumor growth of IRF1-KO cells. In addition, we found that loss of IRF1 in tumor cells could decrease the IFN?-induced expression of PD-L1. To examine if IRF1 can be a target for cancer immunotherapy, we attempted to comprehensively identify genes that are specifically regulated by IRF1 in tumor cells that contribute to the tumor progression and the suppression of immune surveillance. Our RNA-seq data suggest that IRF1 regulates not only the expression of immune inhibitory ligands, but also the production of class I MHC molecules. Overall design: B16-F10 WT and IRF1-KO cells were intradermally injected into C57BL/6 mice. Tumors were harvested at day 12 post injection, and subjected to dissocation into single cell suspension. Tumor cells were negatively selected by anti-CD45 and anti-CD31, and positively selected by anti-CD105. The purified tumor cells were subjected to RNA-seq analysis.