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A distinct gene module for dysfunction uncoupled from activation in tumor-infiltrating T cells
Meromit Singer, Chao Wang, Le Cong, Nemanja D. Marjanovic, Monika S. Kowalczyk, Huiyuan Zhang, Jackson Nyman, Kaori Sakuishi, Sema Kurtulus, David Gennert, Junrong Xia, John Y. H. Kwon, James Nevin, Rebecca H. Herbst, Itai Yanai, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev, Ana C. Anderson
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct ene module for T cell dysfunction that can be uncoupled from T cell activation.