RNA-seq of CT26 cells and tumors treated with or without Midostaurin
Immune checkpoint inhibitor therapy has demonstrated efficacy in a variety of tumors. However, due to the high heterogeneity of colorectal cancer, the clinical efficacy of ICB in the treatment of this disease remains quite limited. Activating mutations of KRAS are detected in 35%–50% of colorectal cancer tissues in clinical. Colorectal cancers with these activating mutations are characterized by an immune desert phenotype and aberrant immune-inflammatory microenvironment. Studies have indicated that oncogene addiction in tumorigenesis (such as KRAS mutation) and non-genetic mechanisms, particularly epigenetic regulation, can synergistically modulate multiple types of plasticity of the tumor microenvironment and tumor cells, but how epigenetic regulators function in the immunosuppressive microenvironment specific to KRAS-mutant colorectal cancer is barely known. In this study, we identify that PHF8 functions as a MHC-I suppressor that limits anti-tumor immunity in KRAS-mutant colorectal cancer. We also find a FDA-approved drug, Midostaurin, which can mimic the phenotype of PHF8 depletion and add to the efficacy of ICB treatment and KRAS inhibition. Overall design: RNA-seq profiling of CT26 cells with or without Midostaurin treatment for 48 h and CT26 subcutaneous tumors treated with or without Midostaurin for 2 weeks