Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer
Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-p...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2528428 |
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| author | Ilseok Choi Kyung-A Kim Sang Cheol Kim Donghwan Park Ki Taek Nam Jun Hyung Cha Seungbyn Baek Junha Cha Hye-Yeong Jo Minsun Jung Melody Y. Zeng Irina Matei Susan Bullman Joong Bae Ahn Yoon Dae Han Han Sang Kim Insuk Lee |
| author_facet | Ilseok Choi Kyung-A Kim Sang Cheol Kim Donghwan Park Ki Taek Nam Jun Hyung Cha Seungbyn Baek Junha Cha Hye-Yeong Jo Minsun Jung Melody Y. Zeng Irina Matei Susan Bullman Joong Bae Ahn Yoon Dae Han Han Sang Kim Insuk Lee |
| author_sort | Ilseok Choi |
| collection | DOAJ |
| description | Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal role of Fn in impairing sIgA induction. We identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised mucosal immunity and increased bacterial infiltration. This IGAM signature effectively stratified Fn-positive patients, suggesting potential for targeted therapeutic approaches. Our findings reveal that Fn disrupts sIgA production, increasing tumor microbial burden and worsening prognosis through chronic inflammation in Fn-positive CRC. |
| format | Article |
| id | doaj-art-028c3d9fdb9543b394e5661fd8655664 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-028c3d9fdb9543b394e5661fd86556642025-08-20T03:50:53ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2528428Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancerIlseok Choi0Kyung-A Kim1Sang Cheol Kim2Donghwan Park3Ki Taek Nam4Jun Hyung Cha5Seungbyn Baek6Junha Cha7Hye-Yeong Jo8Minsun Jung9Melody Y. Zeng10Irina Matei11Susan Bullman12Joong Bae Ahn13Yoon Dae Han14Han Sang Kim15Insuk Lee16Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaYonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDivision of Healthcare and Artificial Intelligence, Department of Precision Medicine, National Institute of Health, Cheongju, Republic of KoreaDepartment of Biomedical Sciences, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Sciences, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaDivision of Healthcare and Artificial Intelligence, Department of Precision Medicine, National Institute of Health, Cheongju, Republic of KoreaDepartment of Pathology, Yonsei University College of Medicine, Seoul, Republic of KoreaChildren’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USAChildren’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USAImmunology, James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USAYonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDivision of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of KoreaYonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaFusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal role of Fn in impairing sIgA induction. We identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised mucosal immunity and increased bacterial infiltration. This IGAM signature effectively stratified Fn-positive patients, suggesting potential for targeted therapeutic approaches. Our findings reveal that Fn disrupts sIgA production, increasing tumor microbial burden and worsening prognosis through chronic inflammation in Fn-positive CRC.https://www.tandfonline.com/doi/10.1080/19490976.2025.2528428Colorectal cancerFusobacterium nucleatumsecretory IgAplasma cell developmenttumor bacterial burden |
| spellingShingle | Ilseok Choi Kyung-A Kim Sang Cheol Kim Donghwan Park Ki Taek Nam Jun Hyung Cha Seungbyn Baek Junha Cha Hye-Yeong Jo Minsun Jung Melody Y. Zeng Irina Matei Susan Bullman Joong Bae Ahn Yoon Dae Han Han Sang Kim Insuk Lee Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer Gut Microbes Colorectal cancer Fusobacterium nucleatum secretory IgA plasma cell development tumor bacterial burden |
| title | Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer |
| title_full | Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer |
| title_fullStr | Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer |
| title_full_unstemmed | Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer |
| title_short | Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer |
| title_sort | secretory iga dysfunction underlies poor prognosis in fusobacterium infected colorectal cancer |
| topic | Colorectal cancer Fusobacterium nucleatum secretory IgA plasma cell development tumor bacterial burden |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2528428 |
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