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VISTA+ Neutrophils Enhance Chemoresistance in High-Grade Serous Ovarian Cancer by Suppressing CD8+ T Cells Infiltration

ABSTRACT: Platinum-based chemoresistance is a primary cause of treatment failure and unfavorable prognosis in high-grade serous ovarian cancer (HGSOC). Although inflammation plays a critical role in chemoresistance, in which neutrophils (Neus) emerge as potent inflammatory regulator across various cancers, the precise mechanisms linking Neus to chemoresistance in HGSOC patients are not well understood. Here, we conducted a retrospective review of HGSOC patients treated with adjuvant chemotherapy, analyzing clinicopathological data and laboratory parameters to show a significant correlation between neutrophil-to-lymphocyte ratio and chemotherapy efficacy. Further experiments revealed an increase in Neus among chemoresistant patients. Proteomic analysis and single-cell RNA sequencing identified VISTA+ Neus as a potent prognostic predictor. In vivo, VISTA blockade reduced VISTA+ Neus infiltration, but increased CD8+T cells within tumor tissues, thereby enhancing chemosensitivity. Our findings highlight the role of VISTA+ Neus in chemoresistance and suggest that targeting these cells could be a novel therapeutic strategy to enhance chemosensitivity in HGSOC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovarian Serous Carcinoma Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Chuying Huo

LAB HEAD: Chuying Huo

PROVIDER: PXD062992 | Pride | 2026-07-01

REPOSITORIES: Pride

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