NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.

Details

Serval ID
serval:BIB_2CBE768B4B2D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.
Journal
Cancer cell
Author(s)
Salomé B., Sfakianos J.P., Ranti D., Daza J., Bieber C., Charap A., Hammer C., Banchereau R., Farkas A.M., Ruan D.F., Izadmehr S., Geanon D., Kelly G., de Real R.M., Lee B., Beaumont K.G., Shroff S., Wang Y.A., Wang Y.C., Thin T.H., Garcia-Barros M., Hegewisch-Solloa E., Mace E.M., Wang L., O'Donnell T., Chowell D., Fernandez-Rodriguez R., Skobe M., Taylor N., Kim-Schulze S., Sebra R.P., Palmer D., Clancy-Thompson E., Hammond S., Kamphorst A.O., Malmberg K.J., Marcenaro E., Romero P., Brody R., Viard M., Yuki Y., Martin M., Carrington M., Mehrazin R., Wiklund P., Mellman I., Mariathasan S., Zhu J., Galsky M.D., Bhardwaj N., Horowitz A.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
12/09/2022
Peer-reviewed
Oui
Volume
40
Number
9
Pages
1027-1043.e9
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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 <sup>+</sup> T cells. In bladder tumors, NKG2A is acquired on CD8 <sup>+</sup> T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A <sup>+</sup> PD-1 <sup>+</sup> CD8 <sup>+</sup> 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 <sup>+</sup> CD8 <sup>+</sup> 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.
Keywords
B7-H1 Antigen/metabolism, CD8-Positive T-Lymphocytes, Histocompatibility Antigens Class I, Humans, NK Cell Lectin-Like Receptor Subfamily C/metabolism, Programmed Cell Death 1 Receptor, Urinary Bladder Neoplasms/therapy, CD8 T cells, HLA class I, NK cells, NKG2A, bladder cancer, checkpoint blockade immunotherapy, immune exhaustion, solid tumors, tumor microenvironment
Pubmed
Create date
27/09/2022 12:49
Last modification date
12/11/2022 6:37
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