Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy.

ABSTRACT: Programmed death-1 homolog (PD-1H) is a coinhibitory molecule that negatively regulates T cell-mediated immune responses. In this study, we determined whether ablation of T cell-associated PD-1H could enhance adoptive T cell therapy in experimental tumor models. The expression of PD-1H is upregulated in activated and tumor-infiltrating CD8+ T cells. Activated CD8+ T cells from PD-1H-deficient (PD-1H-KO) mice exhibited increased cell proliferation, cytokine production, and antitumor activity in vitro. Adoptive transfer of PD-1H-KO CD8+ T cells resulted in the regression of established syngeneic mouse tumors. Similar results were obtained when PD-1H was ablated in T cells by CRISPR/Cas9-mediated gene silencing. Furthermore, ablation of PD-1H in CAR-T cells significantly improved their antitu

SUBMITTER: Hu L 

PROVIDER: S-EPMC8855794 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature