VISTA promotes the metabolism and differentiation of myeloid-derived suppressor cells by STAT3 and polyamine-dependent mechanisms

• DOI: 10.1016/j.celrep.2023.113661
• Publication Date: 2024-01-04T00:57:47Z
• Authors: Keman Zhang; Amin Zakeri; Tyler Alban; Juan Dong; Hieu M. Ta; Ajay H. Zalavadia; Andrelie Branicky; Haoxin Zhao; Ivan Juric; Hana Husic; Prerana B. Partha...; Amit Rupani; Judy A. Drazba; Abhishek A. Chakr...; Stanley Ching-Che...; Timothy Chan; Stefanie Avril; Li Lily Wang
• Keywords: Polyamine; Myeloid-derived Suppressor Cell

Myeloid-derived suppressor cells (MDSCs) impair antitumor immune responses. Identifying regulatory circuits during MDSC development may bring new opportunities for therapeutic interventions. We report that the V-domain of T cell activation (VISTA) functions as a key enabler differentiation. VISTA deficiency reduced STAT3 and STAT3-dependent production polyamines, which causally impaired mitochondrial respiration expansion. In both mixed bone marrow (BM) chimera mice myeloid-specific conditional knockout mice, significantly tumor-associated MDSCs but expanded monocyte-derived dendritic (DCs) enhanced cell-mediated tumor control. Correlated expression arginase-1 (ARG1), enzyme supporting polyamine biosynthesis, was observed in multiple human cancer types. endometrial cancer, co-expression ARG1 on myeloid is associated with poor survival. Taken together, these findings unveil VISTA/polyamine axis central regulator differentiation warrant therapeutically targeting this immunotherapy.