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

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⁺ 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 a

SUBMITTER: Salome B 

PROVIDER: S-EPMC9479122 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature