دورية أكاديمية
NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.
| العنوان: | NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer. |
|---|---|
| المؤلفون: | Salomé, Bérengère, Sfakianos, John P, Ranti, Daniel, Daza, Jorge, Bieber, Christine, Charap, Andrew, Hammer, Christian, Banchereau, Romain, Farkas, Adam M, Ruan, Dan Fu, Izadmehr, Sudeh, Geanon, Daniel, Kelly, Geoffrey, de Real, Ronaldo M, Lee, Brian, Beaumont, Kristin G, Shroff, Sanjana, Wang, Yuanshuo A, Wang, Ying-Chih, Thin, Tin Htwe, Garcia-Barros, Monica, Hegewisch-Solloa, Everardo, Mace, Emily M, Wang, Li, O'Donnell, Timothy, Chowell, Diego, Fernandez-Rodriguez, Ruben, Skobe, Mihaela, Taylor, Nicole, Kim-Schulze, Seunghee, Sebra, Robert P, Palmer, Doug, Clancy-Thompson, Eleanor, Hammond, Scott, Kamphorst, Alice O, Malmberg, Karl-Johan, Marcenaro, Emanuela, Romero, Pedro, Brody, Rachel, Viard, Mathias, Yuki, Yuko, Martin, Maureen, Carrington, Mary, Mehrazin, Reza, Wiklund, Peter, Mellman, Ira, Mariathasan, Sanjeev, Zhu, Jun, Galsky, Matthew D, Bhardwaj, Nina, Horowitz, Amir |
| المصدر: | Cancer Cell ; ISSN:1878-3686 ; Volume:40 ; Issue:9 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2022 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | CD8 T cells, HLA class I, NK cells, NKG2A, bladder cancer, checkpoint blockade immunotherapy, immune exhaustion, solid tumors, tumor microenvironment |
| الوصف: | 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. HLA-ABC expression by bladder tumors is progressively diminished as disease progresses, framing the importance of targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner. Overall, our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1016/j.ccell.2022.08.005Test; https://pubmed.ncbi.nlm.nih.gov/36099881Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479122Test/ |
| DOI: | 10.1016/j.ccell.2022.08.005 |
| الإتاحة: | https://doi.org/10.1016/j.ccell.2022.08.005Test https://pubmed.ncbi.nlm.nih.gov/36099881Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479122Test/ |
| حقوق: | Copyright © 2022 Elsevier Inc. All rights reserved. |
| رقم الانضمام: | edsbas.6D9B9900 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ccell.2022.08.005 |
|---|