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N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner

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Abstract

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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Authors and Affiliations

  1. Department of Urology, Shengjing Hospital of China Medical University, 110000, Shenyang City, Liaoning Province, China

    Yibing Wang, Peng Jin & Xia Wang

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  1. Yibing Wang
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  2. Peng Jin
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  3. Xia Wang
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Contributions

Yibing Wang, Peng Jin performed the assays and wrote the main manuscript and prepared Figs. 1, 2, 3, 4, 5 and 6. Xia Wang was responsible for the funding. All authors reviewed the manuscript.

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Correspondence to Xia Wang.

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Written informed consent was obtained from each patient, and the study had been approved by the Ethical Committee of Shengjing Hospital of China Medical University.

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Wang, Y., Jin, P. & Wang, X. N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner. Apoptosis 29, 142–153 (2024). https://doi.org/10.1007/s10495-023-01885-7

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