Microbiota-driven antitumour immunity mediated by dendritic cell migration

Nina Yi-Tzu Lin, Shota Fukuoka, Shohei Koyama, Daisuke Motooka, Dieter M. Tourlousse, Yuko Shigeno, Yuki Matsumoto, Hiroyuki Yamano, Kazutoshi Murotomi, Hideyuki Tamaki, Takuma Irie, Eri Sugiyama, Shogo Kumagai, Kota Itahashi, Tokiyoshi Tanegashima, Kaori Fujimaki, Sachiko Ito, Mariko Shindo, Takahiro Tsuji, Hiroaki Wake, Keisuke Watanabe, Yuka Maeda, Tomohiro Enokida, Makoto Tahara, Riu Yamashita, Takao Fujisawa, Motoo Nomura, Akihito Kawazoe, Koichi Goto, Toshihiko Doi, Kohei Shitara, Hiroyuki Mano, Yuji Sekiguchi, Shota Nakamura, Yoshimi Benno () and Hiroyoshi Nishikawa ()
Additional contact information
Nina Yi-Tzu Lin: National Cancer Center Research Institute
Shota Fukuoka: National Cancer Center Research Institute
Shohei Koyama: National Cancer Center Research Institute
Daisuke Motooka: Osaka University
Dieter M. Tourlousse: National Institute of Advanced Industrial Science and Technology (AIST)
Yuko Shigeno: RIKEN Cluster for Science Technology and Innovation Laboratory
Yuki Matsumoto: Osaka University
Hiroyuki Yamano: Osaka University
Kazutoshi Murotomi: National Institute of Advanced Industrial Science and Technology (AIST)
Hideyuki Tamaki: National Institute of Advanced Industrial Science and Technology (AIST)
Takuma Irie: National Cancer Center Research Institute
Eri Sugiyama: National Cancer Center Research Institute
Shogo Kumagai: National Cancer Center Research Institute
Kota Itahashi: National Cancer Center Research Institute
Tokiyoshi Tanegashima: National Cancer Center Research Institute
Kaori Fujimaki: Nagoya University Graduate School of Medicine
Sachiko Ito: Nagoya University Graduate School of Medicine
Mariko Shindo: Nagoya University Graduate School of Medicine
Takahiro Tsuji: Nagoya University Graduate School of Medicine
Hiroaki Wake: Nagoya University Graduate School of Medicine
Keisuke Watanabe: National Cancer Center Research Institute
Yuka Maeda: National Cancer Center Research Institute
Tomohiro Enokida: National Cancer Center Hospital East
Makoto Tahara: National Cancer Center Hospital East
Riu Yamashita: National Cancer Center
Takao Fujisawa: National Cancer Center Hospital East
Motoo Nomura: Kyoto University
Akihito Kawazoe: National Cancer Center Hospital East
Koichi Goto: National Cancer Center Hospital East
Toshihiko Doi: National Cancer Center Hospital East
Kohei Shitara: National Cancer Center Hospital East
Hiroyuki Mano: National Cancer Center Research Institute
Yuji Sekiguchi: National Institute of Advanced Industrial Science and Technology (AIST)
Shota Nakamura: Osaka University
Yoshimi Benno: RIKEN Cluster for Science Technology and Innovation Laboratory
Hiroyoshi Nishikawa: National Cancer Center Research Institute

Nature, 2025, vol. 644, issue 8078, 1058-1068

Abstract: Abstract Gut microbiota influence the antitumour efficacy of immune checkpoint blockade1–6, 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 death 1 (PD-1) blockade augmented antitumour responses in mice. YB328 activated tumour-specific CD8+ T cells 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+ T cells 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+ T cells that respond to diverse tumour antigens.

Date: 2025
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DOI: 10.1038/s41586-025-09249-8

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