| First Author | Hu L | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 2 | PubMed ID | 34905507 |
| Mgi Jnum | J:343954 | Mgi Id | MGI:6884996 |
| Doi | 10.1172/jci.insight.148247 | Citation | Hu L, et al. (2022) Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy. JCI Insight 7(2):e148247 |
| abstractText | 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 antitumor activity against human xenografts in vivo. Our results indicate that T cell-associated PD-1H could suppress immunity in the tumor microenvironment and that targeting PD-1H may improve T cell adoptive immunotherapy. |
