PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1⁺CD38^hi cells and anti-PD-1 resistance.

ABSTRACT: Understanding resistance to antibody to programmed cell death protein 1 (PD-1; anti-PD-1) is crucial for the development of reversal strategies. In anti-PD-1-resistant models, simultaneous anti-PD-1 and vaccine therapy reversed resistance, while PD-1 blockade before antigen priming abolished therapeutic outcomes. This was due to induction of dysfunctional PD-1⁺CD38^hi CD8⁺ cells by PD-1 blockade in suboptimally primed CD8 cell conditions induced by tumors. This results in erroneous T cell receptor signaling and unresponsiveness to antigenic restimulation. On the other hand, PD-1 blockade of optimally primed CD8 cells prevented the induction of dysfunctional CD8 cells, reversing resistance. Depleting PD-1⁺CD38^hi CD8⁺ cells enh

SUBMITTER: Verma V 

PROVIDER: S-EPMC7472661 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature