Sensitization of Tumor Cells to IFNy-Mediated Cell Death

Abstract There is increasing evidence that immunotherapies make tumor cells more vulnerable to the host’s own immune system can lead long-term and durable remission. To date, only a small percentage of cancer patients have benefited from this approach advances in field will likely come greater understanding interaction between their targets. T are critical successful anti-tumor response due ability directly lyse by releasing cytolytic granules, produce inflammatory cytokines, such as interferon gamma (IFNγ). IFNγ has several functions an response. On cell side, major driver Th1 differentiation leads activation NK cells. enhance MHC class I presentation but also inhibitory receptors PD-1. However, it not clear whether cytotoxic for If case, selection pressure exerted cells, may acquired mechanisms protect themselves against possibility. Thus, hypothesized normally resistant killing be sensitized if death protection disabled. In preliminary studies using B16F1 murine melanoma model, we found while wild-type (WT) were completely resistant, with knockouts two kinases (DKO) became highly IFNγ-mediated apoptotic death. Furthermore, DKO tumors easily killed IFNγ-dependent manner. These findings provide insight into potential targets therapeutic intervention immune-mediated destruction tumors.