Silencing fatty acid binding protein 5 inhibits prostaglandin E2 and activates CD8 T cells in castration-resistant prostate cancer.

Prostate cancer (PCa) frequently progresses to incurable castration-resistant prostate cancer (CRPC) following androgen deprivation therapy. The immunosuppressive tumor microenvironment limits the efficacy of immunotherapy in CRPC. Fatty acid-binding protein 5 (FABP5) is highly expressed in PCa; however, its role in tumor-associated immune suppression remains poorly defined. This study investigated the effects of FABP5 silencing on tumor proliferation and cluster of differentiation (CD)8+ T cell activity in PCa. FABP5-silenced RM-1 cells were co-cultured with CD8+ T cells, and tumor cell proliferation and T cell differentiation were assessed using Cell Counting Kit-8 assays, colony formation assays, and flow cytometry. In vivo tumor-bearing mouse models were established to evaluate the effect of FABP5 silencing on tumor growth and CD8+ T cell differentiation. Enzyme-linked immunosorbent assays and western blotting were used to analyze cytokine production and protein expression in cells and tumor tissues. Silencing FABP5 significantly reduced RM-1 cell viability and enhanced CD8+ T-cell cytotoxic activity, as evidenced by increased proportions of interferon gamma (IFN-γ)+, CD107a+, and tumor necrosis factor (TNF)-α+ CD8+ T cells, along with elevated secretion of IFN-γ, perforin, and granzyme B. These effects were accompanied by decreased levels of prostaglandin E2 (PGE2) and microsomal prostaglandin E synthase-1 (mPGES-1). In vivo, FABP5 depletion suppressed tumor growth, promoted CD8+ T cell differentiation, and reduced PGE2, mPGES-1, PD-L1, and PCNA expression in tumor tissues. Collectively, these findings demonstrate that FABP5 depletion inhibits PCa proliferation and alleviates immune suppression by activating CD8+ T cells, highlighting FABP5 as a potential therapeutic target for CRPC.