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.
- 1Postgraduate Department, Affiliated Tumor Hospital of the Third Clinical Medical College, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830011, P.R. China.
- 2Department of Gynecology, Affiliated Tumor Hospital of the Third Clinical Medical College, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830011, P.R. China.
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.
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BibTeX
@article{ma2026expression,
title = {{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.}},
author = {Yan Ma and Yidan Xu and Chunxia Yu and Huatuo Wu and Li Li},
journal = {Oncology reports},
year = {2026},
month = oct,
doi = {10.3892/or.2026.9206},
url = {https://europepmc.org/article/MED/42852629},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Yan Ma
AU - Yidan Xu
AU - Chunxia Yu
AU - Huatuo Wu
AU - Li Li
PY - 2026
DA - 2026/10/09
JO - Oncology reports
DO - 10.3892/or.2026.9206
UR - https://europepmc.org/article/MED/42852629
AB - 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.
SN - 1021-335X
SN - 1791-2431
ER -