VISTA+ follicular regulatory T cells modulate the function of effector immune cells: implications for ovarian cancer immune escape
Year: 2025
Type: article
Abstract: 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 toward 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.
Source: Frontiers in Immunology
Authors: Yan Ma, Yidan Xu, Chunxia Yu, Huatuo Wu, Li Li
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4416775713