甲硫氨酸限制引起的硫元素缺乏通过肠道微生物部分损害抗肿瘤免疫功能。
Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota.
发表日期：2023 Aug 03
作者：
Ming Ji, Xiaojiang Xu, Qing Xu, Yun-Chung Hsiao, Cody Martin, Svetlana Ukraintseva, Vladimir Popov, Konstantin G Arbeev, Tom A Randall, Xiaoyue Wu, Liz M Garcia-Peterson, Juan Liu, Xin Xu, M Andrea Azcarate-Peril, Yisong Wan, Anatoliy I Yashin, Karthik Anantharaman, Kun Lu, Jian-Liang Li, Igor Shats, Xiaoling Li
来源：
Epigenetics & Chromatin
摘要：
甲硫氨酸（MR）是含硫的必需氨基酸，据报道，限制MR可以抑制肿瘤生长并提高在几种临床前期环境中的治疗反应。然而，在完整免疫系统情况下，MR如何影响癌症进展还不清楚。在这里，我们报告了在免疫功能受损的小鼠中抑制肿瘤生长的同时，MR可以减少T细胞的数量，加重肿瘤生长，并损害免疫治疗对肿瘤的反应，这在免疫功能健全的雄性和雌性小鼠中得到验证。机制上，MR降低了微生物产生的硫化氢，而硫化氢对免疫细胞的存活和激活至关重要。膳食补充硫化氢给体或前体，或者甲硫氨酸可以刺激抗肿瘤免疫并抑制肿瘤进展。我们的研究揭示了MR、硫缺乏和抗肿瘤免疫之间意想不到的负面相互作用，并进一步揭示了肠道菌群在介导这种相互作用中的重要作用。我们的研究表明，MR可能的抗癌益处需要同时考虑菌群和免疫系统。© 2023。这是美国政府工作，未受版权保护；可能适用外国版权保护。
Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact immune system is unknown. Here we report that while inhibiting cancer growth in immunocompromised mice, MR reduces T cell abundance, exacerbates tumour growth and impairs tumour response to immunotherapy in immunocompetent male and female mice. Mechanistically, MR reduces microbial production of hydrogen sulfide, which is critical for immune cell survival/activation. Dietary supplementation of a hydrogen sulfide donor or a precursor, or methionine, stimulates antitumour immunity and suppresses tumour progression. Our findings reveal an unexpected negative interaction between MR, sulfur deficiency and antitumour immunity and further uncover a vital role of gut microbiota in mediating this interaction. Our study suggests that any possible anticancer benefits of MR require careful consideration of both the microbiota and the immune system.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.