A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy
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 parti...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55388-3 |
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| author | 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 Insuk Lee |
| author_facet | 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 Insuk Lee |
| author_sort | Chan Yeong Kim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-343a89effa8d4c65b8cf8813b8a50d9f |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-343a89effa8d4c65b8cf8813b8a50d9f2025-08-20T02:39:38ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-55388-3A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapyChan Yeong Kim0Dong Jin Park1Beung Chul Ahn2Seungbyn Baek3Min Hee Hong4Linh Thanh Nguyen5Sun Ha Hwang6Nayeon Kim7Daniel Podlesny8Askarbek Orakov9Christian Schudoma10Shahriyar Mahdi Robbani11Hyo Sup Shim12Hong In Yoon13Chang Young Lee14Seong Yong Park15Dongeun Yong16Mina Han17Peer Bork18Byoung Choul Kim19Sang-Jun Ha20Hye Ryun Kim21Insuk Lee22Department of Biotechnology, College of Life Science and Biotechnology, Yonsei UniversityBrain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei UniversityDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of MedicineDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei UniversityDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of MedicineDepartment of Nano-bioengineering, Incheon National UniversityDepartment of Nano-bioengineering, Incheon National UniversityDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei UniversityEuropean Molecular Biology Laboratory, Molecular Systems Biology UnitEuropean Molecular Biology Laboratory, Molecular Systems Biology UnitEuropean Molecular Biology Laboratory, Molecular Systems Biology UnitEuropean Molecular Biology Laboratory, Molecular Systems Biology UnitDepartment of Pathology, Yonsei University College of MedicineDepartment of Radiation Oncology, Yonsei University College of MedicineDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of MedicineDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of MedicineDepartment of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of MedicineDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of MedicineEuropean Molecular Biology Laboratory, Molecular Systems Biology UnitDepartment of Nano-bioengineering, Incheon National UniversityBrain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei UniversityDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of MedicineDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55388-3 |
| spellingShingle | 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 Insuk Lee A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy Nature Communications |
| title | A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy |
| title_full | A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy |
| title_fullStr | A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy |
| title_full_unstemmed | A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy |
| title_short | A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy |
| title_sort | conserved pilin from uncultured gut bacterial clade tanb77 enhances cancer immunotherapy |
| url | https://doi.org/10.1038/s41467-024-55388-3 |
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