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Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy.
Cheng, Siyuan; Han, Zihan; Dai, Die; Li, Fang; Zhang, Xiaotian; Lu, Ming; Lu, Zhihao; Wang, Xicheng; Zhou, Jun; Li, Jian; Guo, Xiaohuan; Song, Panwei; Qiu, Chuangzhao; Shen, Wei; Zhang, Qi; Zhu, Ning; Wang, Xi; Tan, Yan; Kou, Yan; Yin, Xiaochen; Shen, Lin; Peng, Zhi.
Afiliación
  • Cheng S; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China; Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing 100
  • Han Z; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China; Department of Colorectal Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
  • Dai D; Xbiome, Shenzhen 518055, China.
  • Li F; Xbiome, Shenzhen 518055, China.
  • Zhang X; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Lu M; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Lu Z; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Wang X; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Zhou J; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Li J; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Guo X; Institute for Immunology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Song P; Institute for Immunology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Qiu C; Xbiome, Shenzhen 518055, China.
  • Shen W; Xbiome, Shenzhen 518055, China.
  • Zhang Q; Xbiome, Shenzhen 518055, China.
  • Zhu N; Xbiome, Shenzhen 518055, China.
  • Wang X; Xbiome, Shenzhen 518055, China.
  • Tan Y; Xbiome, Shenzhen 518055, China.
  • Kou Y; Xbiome, Shenzhen 518055, China.
  • Yin X; Xbiome, Shenzhen 518055, China. Electronic address: yinxiaochen@xbiome.com.
  • Shen L; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: shenlin@bjm
  • Peng Z; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: zhipeng@bjm
Cell Rep Med ; 5(1): 101355, 2024 01 16.
Article en En | MEDLINE | ID: mdl-38194971
ABSTRACT
Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines of patients with MSI-H/dMMR gastrointestinal cancer (N = 77) at baseline and during the treatment. We identify a number of microbes (e.g., Porphyromonadaceae) and metabolites (e.g., arginine) highly associated with primary resistance to immunotherapy. An independent validation cohort (N = 39) and mouse model are used to further confirm our findings. A predictive machine learning model for primary resistance is also built and achieves an accuracy of 0.79 on the external validation set. Furthermore, several microbes are pinpointed that gradually changed during the process of acquired resistance. In summary, our study demonstrates the essential role of gut microbiome in drug resistance, and this can be utilized as a preventative diagnosis tool and therapeutic target in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Neoplasias Encefálicas / Neoplasias Colorrectales / Microbioma Gastrointestinal / Neoplasias Gastrointestinales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Neoplasias Encefálicas / Neoplasias Colorrectales / Microbioma Gastrointestinal / Neoplasias Gastrointestinales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos