Microbiota-driven antitumour immunity mediated by dendritic cell migration

Gut microbiota influence the antitumour efficacy of immune checkpoint blockade<sup>1-6</sup>, 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<sup>+</sup> T cells through the stimulation of CD103<sup>+</sup>CD11b<sup>-</sup> 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<sup>+</sup>CD11b<sup>-</sup> cDCs showed prolonged engagement with tumour-specific CD8<sup>+</sup> 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<sup>+</sup>CD11b<sup>-</sup> 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<sup>+</sup>CD11b<sup>-</sup> cDCs to increase the number of CD8<sup>+</sup> T cells that respond to diverse tumour antigens.

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Journal
Nature
Published
2025-07-14
DOI
https://doi.org/10.1038/s41586-025-09249-8
Citations
32
Primary Topic
Immunotherapy and Immune Responses
Type
article
Field-Weighted Citation Impact
25.52
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article

Microbiota-driven antitumour immunity mediated by dendritic cell migration

Toshihiko Doi, Daisuke Motooka, Shota Fukuoka, Takuma Irie et al.
32 citations
Nature
Immunotherapy and Immune Responses
25.52
article

Microbiota-driven antitumour immunity mediated by dendritic cell migration

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

Abstract

Gut microbiota influence the antitumour efficacy of immune checkpoint blockade<sup>1-6</sup>, 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<sup>+</sup> T cells through the stimulation of CD103<sup>+</sup>CD11b<sup>-</sup> 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<sup>+</sup>CD11b<sup>-</sup> cDCs showed prolonged engagement with tumour-specific CD8<sup>+</sup> 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<sup>+</sup>CD11b<sup>-</sup> 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<sup>+</sup>CD11b<sup>-</sup> cDCs to increase the number of CD8<sup>+</sup> T cells that respond to diverse tumour antigens.

NatureVol. 644(8078)
Saitama Institute of Technology (JP), Kyoto University (JP), National Cancer Centre Japan (JP), Immunité et Cancer (FR), Chiba Cancer Center (JP), Innovation Cluster (Canada) (CA), National Cancer Center Hospital East (JP), National Cancer Research Institute (GB), Nagoya University (JP), National Institute of Advanced Industrial Science and Technology (JP), Kindai University (JP), The University of Osaka (JP)
Reduced inequalities
Openalex Percentile: Top 0%
Immunotherapy and Immune Responses
25.52
DOIOpen Access PDFOpenAlex
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