小柯机器人

浙江大学王良静等研究人员合作发现，微生物代谢物通过调节泛癌中的T细胞干性提高免疫疗法疗效。这一研究成果于2024年3月14日在线发表在国际学术期刊《细胞》上。

研究人员报告了共生乳酸杆菌约氏乳杆菌的丰度与免疫检查点阻断（ICB）反应性呈正相关。补充约氏乳杆菌或色氨酸衍生代谢产物吲哚-3-丙酸（IPA）可增强CD8⁺ T细胞介导的αPD-1免疫疗法的疗效。

从机理上讲，约氏乳杆菌与生孢梭菌合作产生了IPA。IPA可调节CD8⁺ T细胞的干性程序，并通过增加Tcf7超级增强区的H3K27乙酰化促进原代衰竭CD8⁺ T细胞（T_pex）的生成。IPA在泛癌症水平上提高了ICB反应性，包括黑色素瘤、乳腺癌和结直肠癌。总之，这些研究结果确定了微生物代谢物-免疫调节途径，并提出了一种潜在的基于微生物的辅助方法来提高免疫疗法的反应性。

据悉，人类癌症的ICB反应与肠道微生物群密切相关。

附：英文原文

Title: Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer

Author: Dingjiacheng Jia, Qiwen Wang, Yadong Qi, Yao Jiang, Jiamin He, Yifeng Lin, Yong Sun, Jilei Xu, Wenwen Chen, Lina Fan, Ruochen Yan, Wang Zhang, Guohong Ren, Chaochao Xu, Qiwei Ge, Lan Wang, Wei Liu, Fei Xu, Pin Wu, Yuhao Wang, Shujie Chen, Liangjing Wang

Issue&Volume: 2024-03-14

Abstract: The immune checkpoint blockade (ICB) response in human cancers is closely linked tothe gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacyof CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breastcancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immuneregulatory pathway and suggest a potential microbial-based adjuvant approach to improvethe responsiveness of immunotherapy.

DOI: 10.1016/j.cell.2024.02.022

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00224-1