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Expression of V‑domain Ig suppressor of T cell activation in ovarian cancer and its regulation of follicular regulatory T‑cell function via the AKT/MAPK pathway

Year: 2026

Type: article

Abstract: The high mortality associated with ovarian cancer is closely linked to immune remodeling within the tumor microenvironment (TME).V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, has attracted increasing attention in tumor immunology; however, its effects on follicular regulatory T (Tfr) cell function remain unclear.The present study examined VISTA expression in ovarian cancer and explored the correlation between VISTA and alterations in the AKT/MAPK pathway in Tfr-like cells.Ovarian cancer tissues from different clinical stages and non-malignant control tissues were analyzed by immunofluorescence, reverse transcription-quantitative PCR and western blotting to assess VISTA expression and its association with FOXP3 + CXCR5 + Tfr-like cell infiltration.Naive CD4 + T cells were differentiated into Tfr-like cells in vitro, and VISTA overexpression and silencing models were used to evaluate cell proliferation, cytokine secretion, and AKT/MAPK pathway activation.VISTA expression increased with ovarian cancer progression and was positively associated with Tfr-like cell infiltration.In vitro, VISTA promoted Tfr-like cell proliferation and the secretion of the anti-inflammatory cytokines interleukin-10 and transforming growth factor beta 1 while suppressing the immune effector molecules interleukin-21 and granzyme B, accompanied by reduced AKT and extracellular signal-regulated kinase 1/2 phosphorylation.Collectively, VISTA is upregulated in ovarian cancer and changes in VISTA expression are associated with enhanced immunosuppressive function of Tfr-like cells as well as altered AKT/MAPK phosphorylation levels.These findings provided new insights into the regulation of the ovarian cancer TME and support further investigation of VISTA-targeted immunotherapy.

Source: Oncology Reports

DOI: 10.3892/or.2026.9206

Authors: Yan Ma, Yidan Xu, Chunxia Yu, Huatuo Wu, Li Li

Institutions: Xinjiang Medical University, Tumor Hospital of Xinjiang Medical University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: National Natural Science Foundation of China