304 Type 1 cytokines promote p16-dependent cancer differentiation

Progressing cancers lose their differentiation, and acquire multiple genomic aberrations treatment resistance, what can be enhanced by tumor necrosis factor (TNF). Yet, T cell-based cancer immune therapies, require interferon (IFN)-γ TNF producing type I cells, to induce regression stable remission from metastatic disease. We therefore analyzed the effect of IFN-γ cells on phenotypic cell in endogenously developing islet RT2 mice. During progression, progressively first glucose transporter 2, then insulin finally synaptophysin, aberrations. Immune therapy with checkpoint inhibitors (ICI), prevented promoted differentiation. This required joint signaling TNF, as ICI neither antigen loss nor acquisition either STAT1- or TNF-receptor1-deficient STAT1-expression was also prevent As differentiation IFN-γ-dependent induction p16, responses promote stabilization p16-dependent established cancers.