There is great interest in understanding the dysfunctional state of T-cells during uncontrolled tumor growth, particular regarding the molecular pathways that regulate this functional state for development of potential therapeutic approaches. Here we apply systematic transcriptomic profiling and analysis to dissect the molecular regulation of dysfunctional CD8+ tumor-filtrating lymphocytes (TILs) in a mice melanoma model. We identified key putative regulators and, through combination with precise genome perturbation, established their causal role in driving the dysfunctional phenotype of CD8+ TILs.

Citation Format: Le Cong, Meromit Singer, Chao Wang, John Kwon, Ana Anderson, Orit Rozenblatt-Rosen, Vijay Kuchroo, Aviv Regev. Combining transcriptomic profiling and genome engineering to dissect regulation of tumor immunology [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B085.