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来自微生物群的酸盐促进FOXO1诱导的干性程序,并保持CD8+T细胞对黑色素瘤的免疫力

Annabell Bachem¹, Michele Clarke¹, Geraldine Kong²

¹Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.

|November 4, 2025

概括

微生物生产的短链脂肪酸 (SCFA),与丁酸盐一样,增强抗黑色素瘤CD8+T细胞免疫力. 这种代谢物产生与在接受免疫检查点阻塞 (ICB) 治疗的黑色素瘤患者中获得更好的结果有关.

科学领域:

免疫学免疫学免疫学
微生物组研究微生物组研究
癌症生物学癌症生物学

背景情况:

微生物群的组成会影响癌症的结果和免疫反应.
CD8+ T 细胞对于抗瘤免疫力至关重要,特别是在黑色素瘤中.

研究的目的:

研究肠道微生物群如何调节CD8+ T细胞免疫力对抗黑色素瘤.
探索微生物代谢物,特别是短链脂肪酸 (SCFA),在抗黑色素瘤T细胞反应中的作用.

主要方法:

黑色素瘤的临床前小鼠模型.
调节微生物SCFA生产的饮食干预措施.
流细胞测量用于分析T细胞群 (CD8+,CD127+).
代谢流量建模和转录分析.

主要成果:

微生物SCFA生产与小鼠自发黑色素瘤控制相关.
饮食诱导的SCFA丰富减少了黑色素瘤的进展,并增加了瘤特异性干状CD8+T细胞.
该SCFA酸盐促进了CD8+T细胞干细胞的生长和分化.
丁酸盐增强了与免疫检查点阻塞 (ICB) 响应相关的CD8+T细胞特征.

结论:

微生物代谢物生产,特别是酸盐等SCFA,在维护干状CD8+T细胞至关重要的抗黑色素瘤免疫力方面发挥着至关重要的作用.
这些发现突出了一个潜在的治疗策略,涉及微生物群调节,以改善癌症免疫治疗结果.

关键词:

CD8 T 细胞 CD8 T 细胞在SCFAs中,SCFAs是最重要的.黄油酸盐黄油酸盐是一种黑色素瘤是一种黑色素瘤.代谢代谢代谢代谢微生物组是一个微生物组.我们的微生物群.树干性树干性

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