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微生物代谢物通过调节T细胞干细胞在泛癌症中增强免疫疗效

Dingjiacheng Jia¹, Qiwen Wang², Yadong Qi¹

¹Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.

|March 15, 2024

概括

肠道细菌 Lactobacillus johnsonii 增强了癌症免疫疗法的反应. 补充这种细菌或其代谢物英多尔-3酸 (IPA) 增强T细胞功能,改善各种癌症的免疫疗效.

科学领域:

免疫学
微生物学
癌症学

背景情况:

肠道微生物群显著影响癌症患者免疫检查点阻塞 (ICB) 治疗的有效性.
特定的微生物物种及其代谢物越来越多地被认为是抗瘤免疫力的关键调节剂.

研究的目的:

研究肠道开始性细菌,特别是Lactobacillus johnsonii在调节ICB治疗反应中的作用.
阐明Lactobacillus johnsonii及其代谢物增强抗瘤免疫力的潜在机制.

主要方法:

在癌症患者中,Lactobacillus johnsonii丰度与ICB反应之间的相关性分析.
在临床前模型中实验补充Lactobacillus johnsonii或英多尔-3-酸 (IPA).
涉及CD8+T细胞表征和表观遗传分析 (H3K27乙化) 的机制研究.

主要成果:

牛乳杆菌的丰度与ICB的响应有正相关性.
补充 Lactobacillus johnsonii 或 IPA 增强了 CD8+ T 细胞介导免疫疗法 (αPD-1).
通过增加Tcf7超增强区的H3K27乙化,IPA调节了CD8+T细胞干细胞,并促进了T细胞 (Tpex) 的产生.
在黑色素瘤,乳腺癌和结直肠癌模型中,IPA在改善ICB反应方面表现出有效性.

结论:

牛乳杆菌和其代谢物IPA代表了一种新的基于微生物的策略来增强癌症免疫疗法.
已确定的微生物代谢物-免疫调节途径为改善患者对ICB的反应提供了潜在的辅助方法.
针对肠道微生物群及其代谢产物有望优化癌症治疗结果.

关键词:

牛乳杆菌约翰尼在 TCF-1 癌症免疫疗法肠道微生物群免疫检查点封锁印度尔-3-酸原始细胞耗尽的CD8 ((+) T细胞三丰的代谢

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