Michael R Schlabach, Sharon Lin, Zachary R Collester, Christopher Wrocklage, Sol Shenker, Conor Calnan, Tianlei Xu, Hugh S Gannon, Leila J Williams, Frank Thompson, Paul R Dunbar, Robert A LaMothe, Tracy E Garrett, Nicholas Colletti, Anja F Hohmann, Noah J Tubo, Caroline P Bullock, Isabelle Le Mercier, Katri Sofjan, Jason J Merkin, Sean Keegan, Gregory V Kryukov, Caroline Dugopolski, Frank Stegmeier, Karrie Wong, Fiona A Sharp, Louise Cadzow, Micah J Benson
Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine CD8+ T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cells (Texprog) in tumors...
December 15, 2023: Journal of Clinical Investigation