Bérengère Salomé, John P Sfakianos, Daniel Ranti, Jorge Daza, Christine Bieber, Andrew Charap, Christian Hammer, Romain Banchereau, Adam M Farkas, Dan Fu Ruan, Sudeh Izadmehr, Daniel Geanon, Geoffrey Kelly, Ronaldo M de Real, Brian Lee, Kristin G Beaumont, Sanjana Shroff, Yuanshuo A Wang, Ying-Chih Wang, Tin Htwe Thin, Monica Garcia-Barros, Everardo Hegewisch-Solloa, Emily M Mace, Li Wang, Timothy O'Donnell, Diego Chowell, Ruben Fernandez-Rodriguez, Mihaela Skobe, Nicole Taylor, Seunghee Kim-Schulze, Robert P Sebra, Doug Palmer, Eleanor Clancy-Thompson, Scott Hammond, Alice O Kamphorst, Karl-Johan Malmberg, Emanuela Marcenaro, Pedro Romero, Rachel Brody, Mathias Viard, Yuko Yuki, Maureen Martin, Mary Carrington, Reza Mehrazin, Peter Wiklund, Ira Mellman, Sanjeev Mariathasan, Jun Zhu, Matthew D Galsky, Nina Bhardwaj, Amir Horowitz
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms...
September 12, 2022: Cancer Cell