Chun-Pu Lin, Pierre L Levy, Astrid Alflen, Georgi Apriamashvili, Maarten A Ligtenberg, David W Vredevoogd, Onno B Bleijerveld, Ferhat Alkan, Yuval Malka, Liesbeth Hoekman, Ettai Markovits, Austin George, Joleen J H Traets, Oscar Krijgsman, Alex van Vliet, Joanna Poźniak, Carlos Ariel Pulido-Vicuña, Beaunelle de Bruijn, Susan E van Hal-van Veen, Julia Boshuizen, Pim W van der Helm, Judit Díaz-Gómez, Hamdy Warda, Leonie M Behrens, Paula Mardesic, Bilal Dehni, Nils L Visser, Jean-Christophe Marine, Gal Markel, William J Faller, Maarten Altelaar, Reuven Agami, Michal J Besser, Daniel S Peeper
Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation...
March 13, 2024: Cancer Cell