PD-1H/VISTA mediates immune evasion in acute myeloid leukemia

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.