tRF-3017b promotes prostate cancer progression by enhancing cell proliferation, CTL resistance, and M2 macrophage polarization.

This research sought to assess the expression pattern and biological function of tRF-3017b in prostate cancer, and to elucidate whether tRF-3017b promotes tumor progression by modulating tumor cell proliferation, cytotoxic T lymphocyte (CTL) resistance, and M2 macrophage polarization through cytokine-mediated STAT3 signaling. The expression of tRF-3017b was examined in 40 paired PCa and adjacent normal tissues using quantitative RT-PCR. LNCaP cells were transfected with tRF-3017b inhibitors to evaluate their proliferative capacity, cytokine secretion, and immune interactions. Co-culture systems were established between LNCaP cells and CTLs or THP-1-derived macrophages. Cell proliferation (CCK-8), cytokine levels (ELISA), macrophage markers (qRT-PCR, immunofluorescence), migration (Transwell assay), and STAT3 activation (Western blot) were systematically analyzed. tRF-3017b levels were markedly elevated in prostate cancer tissues relative to paired normal counterparts (P < 0.001). Silencing tRF-3017b significantly inhibited LNCaP cell proliferation and reduced the secretion of immunosuppressive cytokines, such as IL-10, TGF-β1, CSF1, and CCL2. In co-culture assays, tRF-3017b knockdown enhanced CTL-mediated cytotoxicity against tumor cells and impaired M2 macrophage polarization, as shown by the diminished expression of ARG1, IL-10, and CD206 and reduced p-STAT3 activation. Our findings suggest that tRF-3017b may contribute to prostate cancer progression by regulating tumor proliferation and immune modulation in vitro, particularly through the cytokine-mediated STAT3 signaling axis. These findings identify tRF-3017b as a novel regulator of tumor–immune crosstalk and a promising therapeutic target for reprogramming the immunosuppressive microenvironment in prostate cancer.