A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy

Chan Yeong Kim, Dong Jin Park, Beung Chul Ahn, Seungbyn Baek, Min Hee Hong, Linh Thanh Nguyen, Sun Ha Hwang, Nayeon Kim, Daniel Podlesny, Askarbek Orakov, Christian Schudoma, Shahriyar Mahdi Robbani, Hyo Sup Shim, Hong In Yoon, Chang Young Lee, Seong Yong Park, Dongeun Yong, Mina Han, Peer Bork, Byoung Choul Kim (), Sang-Jun Ha (), Hye Ryun Kim () and Insuk Lee ()
Additional contact information
Chan Yeong Kim: Yonsei University
Dong Jin Park: Yonsei University
Beung Chul Ahn: Yonsei University College of Medicine
Seungbyn Baek: Yonsei University
Min Hee Hong: Yonsei University College of Medicine
Linh Thanh Nguyen: Incheon National University
Sun Ha Hwang: Incheon National University
Nayeon Kim: Yonsei University
Daniel Podlesny: Molecular Systems Biology Unit
Askarbek Orakov: Molecular Systems Biology Unit
Christian Schudoma: Molecular Systems Biology Unit
Shahriyar Mahdi Robbani: Molecular Systems Biology Unit
Hyo Sup Shim: Yonsei University College of Medicine
Hong In Yoon: Yonsei University College of Medicine
Chang Young Lee: Yonsei University College of Medicine
Seong Yong Park: Yonsei University College of Medicine
Dongeun Yong: Yonsei University College of Medicine
Mina Han: Yonsei University College of Medicine
Peer Bork: Molecular Systems Biology Unit
Byoung Choul Kim: Incheon National University
Sang-Jun Ha: Yonsei University
Hye Ryun Kim: Yonsei University College of Medicine
Insuk Lee: Yonsei University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome’s influence on ICB efficacy is of particular interest due to its modifiability through various interventions. However, gut microbiome biomarkers for ICB response have been inconsistent across different studies. Here, we identify TANB77, an uncultured and distinct bacterial clade, as the most consistent responder-enriched taxon through meta-analysis of ten independent ICB recipient cohorts. Traditional taxonomy fails to distinguish TANB77 from unrelated taxa, leading to its oversight. Mice with higher gut TANB77 abundance, either naturally or through transplantation, show improved response to anti-PD-1 therapy. Additionally, mice injected with TANB77-derived pilin-like protein exhibit improved anti-PD-1 therapy response, providing in vivo evidence for the beneficial role of the pilin-like protein. These findings suggest that pilins from the TANB77 order may enhance responses to ICB therapy across diverse cohorts of cancer patients.

Date: 2024
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DOI: 10.1038/s41467-024-55388-3

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