Pan-cancer analysis identifies FKBP10 as a regulator of tumor immunosuppression and therapeutic response

Tumor immune regulation depends on interactions between intrinsic molecular mechanisms, tumor cell metabolic states, and the immune microenvironment. The ER‑localized isomerase FK506‑binding protein 10 (FKBP10) is essential for extracellular matrix homeostasis, but its systemic role in cancer immune regulation and therapeutic response remains unclear.

A pan‑cancer analysis of 33 TCGA tumor types integrated copy number variation, DNA methylation, and mutation data to elucidate FKBP10 regulation. ESTIMATE, ImmuCellAI, and TIMER2 assessed immune infiltration and immunosuppressive phenotypes, and pathway enrichment identified FKBP10‑related metabolic reprogramming, ECM remodeling, EMT, and programmed cell death signals. Therapeutic response was evaluated using breast cancer in vitro assays and GDSC drug sensitivity data.

FKBP10 was significantly upregulated in multiple cancers, especially breast and renal carcinoma, and strongly associated with poor prognosis. Its high expression was mainly driven by promoter hypomethylation and copy number amplification. FKBP10‑high tumors showed enhanced ECM remodeling, metabolic reprogramming, and apoptosis resistance, accompanied by an immunosuppressive microenvironment with reduced cytotoxic T cells and enrichment of myeloid‑derived suppressor cells and cancer‑associated fibroblasts. High FKBP10 expression also correlated with decreased sensitivity to several chemotherapeutic agents. In vitro experiments confirmed that FKBP10 promotes tumor cell proliferation and clonogenicity.

FKBP10 is closely linked to tumor progression and treatment response by contributing to metabolic reprogramming, immunosuppressive microenvironment modulation, and programmed cell death regulation, supporting its potential as a biomarker and therapeutic target for predicting prognosis, treatment response, and immunotherapy outcomes.