YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells
| العنوان: | YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells |
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| المؤلفون: | Shoubao Ma, Baofa Sun, Songqi Duan, Jingjing Han, Tasha Barr, Jianying Zhang, Marc B. Bissonnette, Marcin Kortylewski, Chuan He, Jianjun Chen, Michael A. Caligiuri, Jianhua Yu |
| المصدر: | Nat Immunol |
| بيانات النشر: | Springer Science and Business Media LLC, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy, Article |
| الوصف: | Despite tumor-associated macrophages (TAMs) playing a key role in shaping the tumor microenvironment (TME), the mechanisms by which TAMs influence the TME and contribute to cancer progression remain unclear. Here, we show that the N(6)-methyladenosine reader YTHDF2 regulates the antitumor functions of TAMs. YTHDF2 deficiency in TAMs suppressed tumor growth by reprogramming TAMs toward an antitumoral phenotype and increasing their antigen cross-presentation ability, which in turn enhanced CD8(+) T cell-mediated antitumor immunity. YTHDF2 deficiency facilitated the reprogramming of TAMs by targeting interferon-γ–STAT1 signaling. The expression of YTHDF2 in TAMs was regulated by interleukin-10–STAT3 signaling. Selectively targeting YTHDF2 in TAMs using a Toll-like receptor 9 agonist-conjugated small interfering RNA reprogrammed TAMs toward an antitumoral phenotype, restrained tumor growth and enhanced the efficacy of PD-L1 antibody therapy. Collectively, our findings describe the role of YTHDF2 in orchestrating TAMs and suggest that YTHDF2 inhibition is an effective approach to enhance cancer immunotherapy. |
| تدمد: | 1529-2916 1529-2908 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c936002dae30bf04154acb757f03be05 https://doi.org/10.1038/s41590-022-01398-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c936002dae30bf04154acb757f03be05 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15292916 15292908 |
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