ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCancer Immunity: From Immunosurveillance to Immune Escape and Therapeutic TargetingView all articles
VISTA⁺ follicular regulatory T cells modulate the function of effector immune cells: implications for ovarian cancer immune escape
Provisionally accepted
- 1Cancer Hospital of Xinjiang Medical University, Urumqi, China
- 2Xinjiang Medical University, Urumqi, China
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Background: As key regulatory cells, the impact of follicular regulatory T (Tfr) cells, whose function is regulated by V-domain Ig suppressor of T cell activation (VISTA), on downstream immune cells remains unclear. These cellular-level regulatory mechanisms are closely associated with the development of immune escape in ovarian cancer, a disease characterized by severe effector immune cell dysfunction in the tumor microenvironment. This study aims to elucidate the regulatory effects of VISTA⁺ Tfr cells on the functions of CD8⁺ T cells, CD4⁺CD25⁻ T cells, and B cells, and to reveal their significance in the immune escape of ovarian cancer. Methods: VISTA-overexpressing and silenced Tfr cell models were constructed in vitro. Through co-culture experiments, CFSE proliferation assays, ELISA, and flow cytometry were employed to investigate the effects of VISTA⁺ Tfr cells on CD8⁺ T cell proliferation, effector cytokine secretion, and activation status; their regulation of CD4⁺CD25⁻ T cell proliferation, cytokine secretion, and Th cell differentiation; and their impact on B cell proliferation and antibody secretion. Results: VISTA⁺ Tfr cells significantly inhibited CD8⁺ T cell proliferation, secretion of effector cytokines (IL-2, IFN-γ), and expression of the activation marker CD69, while upregulating their exhaustion molecules (PD-1, CTLA-4). They skewed the differentiation of CD4⁺CD25⁻ T cells towards a Th2 phenotype and suppressed Th1 and Th17 cell differentiation. Furthermore, they specifically inhibited IgE secretion by B cells, with no significant effect on other antibodies. Conclusion: VISTA⁺ Tfr cells multi-dimensionally suppress the function of effector immune cells, providing experimental evidence for the potential role of VISTA-targeted strategies in improving anti-tumor immune responses in ovarian cancer.
Keywords: VISTA⁺ follicular regulatory T cells, ovarian cancer, CD8+ T cells, T helper cells, B cells, immune escape
Received: 12 Sep 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Ma, Xu, Yu, Wu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Li Li, lili202589@outlook.com
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