High expression of VISTA on M-MDSCs is associated with immunosuppression and predicts poor prognosis in acute myeloid leukemia

V-domain Ig suppressor of T-cell activation (VISTA), as a novel immune checkpoint, is highly expressed on monocytic myeloid-derived suppressor cells (M-MDSCs). In patients with acute myeloid leukemia (AML), the prognostic significance of VISTA on bone marrow-infiltrated M-MDSCs is not clear. In this study, we performed flow cytometry to test VISTA expression on M-MDSCs in bone marrow of 54 patients with newly diagnosed AML and 6 healthy individuals. The percentage of VISTA + M-MDSCs were significantly higher in AML patients than in healthy donors ( P = 0.0003). Higher percentage of VISTA + M-MDSCs correlated with higher cumulative incidence of relapse (CIR) ( P = 0.008), shorter overall survival ( P = 0.0043) and shorter event-free survival ( P = 0.0013). High expression of VISTA on M-MDSCs independently predicted a higher CIR ( P = 0.025). In addition, single cell RNA sequencing analysis revealed that VISTA + M-MDSCs exhibited potent immunosuppressive function, characterized by high production of IL-10 and reactive oxygen species. By combining differential expression analysis and virtual knockout algorithm, we identified ANXA1 and VCAN as the potential downstream targets of VISTA in M-MDSCs. In conclusion, VISTA + M-MDSC is a highly immunosuppressive population in bone marrow microenvironment of AML patients and correlates with adverse clinical outcomes.