A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy
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.
Authors
- Beung‐Chul Ahn (ORCID: https://orcid.org/0000-0002-2579-2791)
- Sang‐Jun Ha (ORCID: https://orcid.org/0000-0002-1192-6031)
- Chan Yeong Kim (ORCID: https://orcid.org/0000-0002-0868-9872)
- Sun Ha Hwang
- Min Hee Hong (ORCID: https://orcid.org/0000-0003-3490-2195)
- Askarbek Orakov (ORCID: https://orcid.org/0000-0001-6823-5269)
- Hyo Sup Shim (ORCID: https://orcid.org/0000-0002-5718-3624)
- Seungbyn Baek (ORCID: https://orcid.org/0000-0002-4039-277X)
- Linh Thanh Nguyen (ORCID: https://orcid.org/0000-0003-0886-2708)
- Insuk Lee (ORCID: https://orcid.org/0000-0003-3146-6180)
- Mina Han
- Hye Ryun Kim (ORCID: https://orcid.org/0000-0002-1842-9070)
- Daniel Podlesny (ORCID: https://orcid.org/0000-0002-5685-0915)
- Byoung Choul Kim (ORCID: https://orcid.org/0000-0001-5101-4339)
- Christian Schudoma (ORCID: https://orcid.org/0000-0003-1157-1354)
- Dongeun Yong (ORCID: https://orcid.org/0000-0002-1225-8477)
- Shahriyar Mahdi Robbani (ORCID: https://orcid.org/0000-0003-0161-0559)
- Peer Bork (ORCID: https://orcid.org/0000-0002-2627-833X)
- Hong In Yoon (ORCID: https://orcid.org/0000-0002-2106-6856)
- Sung Yong Park (ORCID: https://orcid.org/0000-0002-5180-3853)
- Dong Jin Park (ORCID: https://orcid.org/0000-0002-2412-5292)
- Chang Young Lee (ORCID: https://orcid.org/0000-0002-2404-9357)
- Nayeon Kim (ORCID: https://orcid.org/0009-0003-6566-3972)
Institutions
- Pohang University of Science and Technology (KR)
- Incheon National University (KR)
- Yonsei University (KR)
- Samsung Medical Center (KR)
- National Cancer Center (US)
- National Cancer Center (KR)
- European Molecular Biology Laboratory (DE)
- Yonsei University Health System (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-27
- DOI
- https://doi.org/10.1038/s41467-024-55388-3
- Citations
- 7
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.68
Funders
- National Research Foundation
- Yonsei University
- Ministry of Trade, Industry and Energy
- National Research Foundation of Korea
- Korea Drug Development Fund
- Ministry of Science and ICT, South Korea
- Samsung Science and Technology Foundation
- Samsung