越来越多的数据和文献表明，肿瘤免疫逃避是肿瘤形成和复发的主要原因。此外，新的发现还表明RNA N6-甲基腺苷（m6A）参与人类癌症的免疫逃避。本研究探讨了m6A阅读器YTHDF1在前列腺癌（PCa）免疫应答中的功能，并探讨了其功能机制。结果报告显示，YTHDF1在PCa样本中上调表达，并与糟糕的临床预后密切相关。在功能上，YTHDF1抑制了CD8+ T细胞对PCa细胞的杀伤活性，并减轻了铁死亡。从机制上看，PD-L1是YTHDF1的靶标，YTHDF1上调了PD-L1 mRNA的转录活性。综上所述，YTHDF1通过提高PD-L1的转录稳定性部分促进了其功能，这对于PCa细胞逃避效应T细胞细胞毒性和CD8+ T细胞介导的铁死亡至关重要。总之，这些发现表明，YTHDF1通过m6A-PD-L1的方式抑制了CD8+ T细胞介导的抗肿瘤免疫和铁死亡，在PCa中，这可能为PCa免疫治疗提供了新的见解。© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.