VISTA promotes the metabolism and differentiation of myeloid-derived suppressor cells by STAT3 and polyamine-dependent mechanisms
Mice, Knockout
STAT3 Transcription Factor
0301 basic medicine
0303 health sciences
QH301-705.5
Myeloid-Derived Suppressor Cells
T-Lymphocytes
CP: Immunology
Article
Mice
Neoplasms
Polyamines
Animals
Humans
Myeloid Cells
Biology (General)
CP: Cancer
DOI:
10.1016/j.celrep.2023.113661
Publication Date:
2024-01-04T00:57:47Z
AUTHORS (18)
ABSTRACT
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 suppressor of T cell activation (VISTA) functions as a key enabler of MDSC differentiation. VISTA deficiency reduced STAT3 activation and STAT3-dependent production of polyamines, which causally impaired mitochondrial respiration and MDSC expansion. In both mixed bone marrow (BM) chimera mice and myeloid-specific VISTA conditional knockout mice, VISTA deficiency significantly reduced tumor-associated MDSCs but expanded monocyte-derived dendritic cells (DCs) and enhanced T cell-mediated tumor control. Correlated expression of VISTA and arginase-1 (ARG1), a key enzyme supporting polyamine biosynthesis, was observed in multiple human cancer types. In human endometrial cancer, co-expression of VISTA and ARG1 on tumor-associated myeloid cells is associated with poor survival. Taken together, these findings unveil the VISTA/polyamine axis as a central regulator of MDSC differentiation and warrant therapeutically targeting this axis for cancer immunotherapy.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (96)
CITATIONS (21)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....