N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner
Springer Science and Business Media LLC - Trang 1-12 - 2023
Tóm tắt
Increasing data and literature have illustrated that tumor immune escape represents a major source of tumor formation and recrudesce. Besides, novel findings also indicate that RNA N6-methyladenosine (m6A) participates in the human cancer immune escape. Here, our study investigated the functions of m6A reader YTHDF1 in prostate cancer (PCa) immune response and explored the functional mechanism. Results reported that YTHDF1 up-regulated in PCa samples and was closely correlated to poor clinical prognosis. Functionally, YTHDF1 inhibited the killing activity of CD8 + T cells to PCa cells, and moreover mitigated the ferroptosis. Mechanistically, PD-L1 acted as the target of YTHDF1, and YTHDF1 upregulated the transcriptional activity of PD-L1 mRNA. Collectively, YTHDF1 promoted functional PD-L1 partially through enhancing its transcriptional stability, which was necessary for PCa cells to evade effector T cell cytotoxicity and CD8 + T cells mediated ferroptosis. In conclusion, these findings indicate that YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in PCa via m6A-PD-L1 manner, which may provide novel insight for PCa immunotherapy.
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