Fibroblast Growth Factor 11 Promotes Immune Escape of Cervical Cancer Cells by Promoting Infiltration of CD4+ T Cells, Particularly Regulatory T Cells.

Abstract

Background: Cervical cancer (CC) is one of the leading gynecological malignancies. Immunotherapy has shown limited efficacy, particularly for advanced, recurrent CC. Consequently, dependable prognostic biomarkers and treatment targets are needed. Methods and Results: In this study, we aimed to determine the association of fibroblast growth factor 11 (FGF11) with prognosis. FGF11 expression was assessed in both tissues and cells through immunohistochemical and immunocytochemical staining. Immune cell infiltration was predicted using Tumor Immune Estimation Resource (TIMER) and TIMER2.0. FGF11 was significantly correlated with prognosis. FGF11 expression was significantly elevated in CC tissues. Moreover, FGF11 expression was significantly higher in SiHa and HeLa cancer cells than in normal H8 cells, particularly SiHa cells. Enrichment analyses suggested that FGF11 may be involved in arachidonic acid and linoleic acid metabolism, indicating roles in epithelial adhesion and cell differentiation. FGF11 correlated positively with CD4⁺ T, regulatory T, and dendritic cells but negatively with CD8⁺ T cells. FGF11 also correlated positively with Cluster of Differentiation 4 (CD4), CD25, Forkhead box P3 (FOXP3), and transforming growth factor β but negatively with human leukocyte antigens. Conclusions: FGF11 may enhance the immune escape abilities of CC cells by promoting CD4⁺ T cell infiltration (particularly regulatory T cells) into the tumor microenvironment, leading to poor prognosis. These findings provide a reference for the exploration of FGF11 as a prognostic biomarker and treatment target in CC.