Pluto Bioinformatics

GSE132926: Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [RNA-Seq]

Bulk RNA sequencing

CD8+cytotoxic T cells play essential roles in anti-tumor immune responses. Here, we performed in vivo screens in CD8+T cells and identified regulators of tumor infiltration and killing, which are directly relevant to cancer immunotherapy. Unlike in vitro screens, the in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8+T cells against cancer in vivo. Immunological characterization in mouse and human CD8+T cells revealed that DHX37 suppresses effector function, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating the NF-kB pathway. These data demonstrated the power of high-throughput in vivo genetic screens for immunotherapy target discovery, and uncovered DHX37 as a functional regulator of CD8+T cells. SOURCE: Ryan,D,Chow (ryan.chow@yale.edu) - Yale University