近日，日本国家癌症中心研究所教授Hiroyoshi Nishikawa及其课题组探明了树突状细胞迁移介导的微生物驱动的抗肿瘤免疫。相关论文发表在2025年7月14日出版的《自然》杂志上。

课题组人员表明，从对程序性细胞死亡有反应的患者的粪便中分离出一种新的细菌基因——人肠微生物（命名为YB328）1（PD-1）阻断增强了小鼠的抗肿瘤反应。YB328激活肿瘤特异性CD8⁺ TCD103⁺CD11b^-传统的树突状细胞（cdc），在肠道暴露后，迁移到肿瘤微环境中。用无反应患者的粪便移植补充YB238治疗小鼠时，PD-1阻断的抗肿瘤效果得到改善。这表明YB328可能以显性方式发挥作用。YB328激活的CD103 ⁺ CD11b^- cDCs与肿瘤特异性CD8⁺ T细胞的结合时间延长并促进PD-1在这些细胞中的表达。

此外，YB238增强PD-1阻断治疗的抗肿瘤效果在多多主题肿瘤模型中被观察到。YB328丰度升高的患者CD103⁺CD11b^-肿瘤中的cDCs对各种类型的PD-1阻断治疗有良好的反应。课题组人员提出肠道微生物群通过加速CD103⁺CD11b^-疾控中心增加CD⁸⁺ T的数量对不同肿瘤抗原有反应的细胞。

研究人员表示，肠道菌群影响免疫检查点阻断剂的抗肿瘤效果，但其作用机制尚未完全阐明。

附：英文原文

Title: Microbiota-driven antitumour immunity mediated by dendritic cell migration

Author: Lin, Nina Yi-Tzu, Fukuoka, Shota, Koyama, Shohei, Motooka, Daisuke, Tourlousse, Dieter M., Shigeno, Yuko, Matsumoto, Yuki, Yamano, Hiroyuki, Murotomi, Kazutoshi, Tamaki, Hideyuki, Irie, Takuma, Sugiyama, Eri, Kumagai, Shogo, Itahashi, Kota, Tanegashima, Tokiyoshi, Fujimaki, Kaori, Ito, Sachiko, Shindo, Mariko, Tsuji, Takahiro, Wake, Hiroaki, Watanabe, Keisuke, Maeda, Yuka, Enokida, Tomohiro, Tahara, Makoto, Yamashita, Riu, Fujisawa, Takao, Nomura, Motoo, Kawazoe, Akihito, Goto, Koichi, Doi, Toshihiko, Shitara, Kohei, Mano, Hiroyuki, Sekiguchi, Yuji, Nakamura, Shota, Benno, Yoshimi, Nishikawa, Hiroyoshi

Issue&Volume: 2025-07-14

Abstract: Gut microbiota influence the antitumour efficacy of immune checkpoint blockade1,2,3,4,5,6, but the mechanisms of action have not been fully elucidated. Here, we show that a new strain of the bacterial genus Hominenteromicrobium (designated YB328) isolated from the faeces of patients who responded to programmed cell death1 (PD-1) blockade augmented antitumour responses in mice. YB328 activated tumour-specific CD8+ Tcells through the stimulation of CD103+CD11b conventional dendritic cells (cDCs), which, following exposure in the gut, migrated to the tumour microenvironment. Mice showed improved antitumour efficacy of PD-1 blockade when treated with faecal transplants from non-responder patients supplemented with YB238. This result suggests that YB328 could function in a dominant manner. YB328-activated CD103+CD11b cDCs showed prolonged engagement with tumour-specific CD8+ Tcells and promoted PD-1 expression in these cells. Moreover, YB238-augmented antitumour efficacy of PD-1 blockade treatment was observed in multiple mouse models of cancer. Patients with elevated YB328 abundance had increased infiltration of CD103+CD11b cDCs in tumours and had a favourable response to PD-1 blockade therapy in various cancer types. We propose that gut microbiota enhance antitumour immunity by accelerating the maturation and migration of CD103+CD11b cDCs to increase the number of CD8+ Tcells that respond to diverse tumour antigens.

DOI: 10.1038/s41586-025-09249-8

Source: https://www.nature.com/articles/s41586-025-09249-8