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

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.