Platinoid drugs augment immunotherapy via histone acetylation of MHCI machinery genes [AT_MC]

Here we show that low dose Oxali, and to a lesser extent other platinoids, can uniquely activate the transcriptional program that controls MHCI antigen processing and presentation. Activation of this program correlates with induction of histone acetylation and enhanced chromatin accessibility. Oxaliplatin also induces NF-kB dependent IFNg receptor 2 (IFNgR2) thereby augmenting the tumor response to exogenous IFNg produced by reinvigorated effector CD8+ T cells. Nuclei/DNA were isolated after 48h treatment of prostate cancer cell line Myc-Cap with Oxaliplatin (2uM), Cisplatin (2uM), IFNg (1000pg), or a combination of Oxali (2uM) + IFNg (1000pg).