FBXL16 regulates TAMs recruitment by mediating cytokine release in gliomas

Gliomas are characterized by an immunosuppressive tumor microenvironment (TME), which significantly limits the efficacy of current immunotherapies. To address this challenge, we explored the role of FBXL16, a gene with distinct expression patterns in nervous system tumors identified through analysis of public databases. Our study utilized clinical sample analysis, survival correlation, in vitro functional assays, and in vivo mouse models to investigate FBXL16's impact on glioma progression. Gene set enrichment analysis (GSEA), immunosuppression profiling, and co-culture assays with flow cytometry validation were employed to elucidate its immunological role, particularly in regulating M2-type tumor-associated macrophage (M2-TAM) recruitment. Our investigation revealed a substantial decrease in FBXL16 expression within glioma tissues, which exhibited and positively correlation with patient survival rates. Overexpression of FBXL16 in glioma cells suppressed proliferation, migration, and invasion, and extended survival in glioma-bearing mice. Mechanistically, FBXL16 regulated the secretion of key immunoregulatory cytokines such as TGF-β, IL-6, IFN-α, and VEGF, thereby disrupting macrophage recruitment to the TME. These findings suggest that FBXL16 attenuates glioma progression by inhibiting cytokine release and limiting TAM recruitment, thus interrupting the immunosuppressive feedback loop within the TME. Our study highlights FBXL16 as a promising immunomodulatory target for glioma therapy, offering new insights into overcoming immunosuppression in gliomas.