| First Author | Kim TK | Year | 2024 |
| Journal | J Clin Invest | Volume | 134 |
| Issue | 3 | PubMed ID | 38060328 |
| Mgi Jnum | J:352241 | Mgi Id | MGI:7580363 |
| Doi | 10.1172/JCI164325 | Citation | Kim TK, et al. (2024) PD-1H/VISTA mediates immune evasion in acute myeloid leukemia. J Clin Invest 134(3):e164325 |
| abstractText | Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics, such as targeted therapy and immunotherapy, including anti-programmed cell death protein (anti-PD) therapy. We demonstrate that programmed death-1 homolog (PD-1H), an immune coinhibitory molecule, is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells express PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell-surface PD-1H by antibody blockade or genetic knockout significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression, and the combination of PD-1H blockade with anti-PD therapy conferred a synergistic antileukemia effect. Our findings provide the basis for PD-1H as a potential therapeutic target for treating human AML. |
