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Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.
Jia, Dingjiacheng; Wang, Qiwen; Qi, Yadong; Jiang, Yao; He, Jiamin; Lin, Yifeng; Sun, Yong; Xu, Jilei; Chen, Wenwen; Fan, Lina; Yan, Ruochen; Zhang, Wang; Ren, Guohong; Xu, Chaochao; Ge, Qiwei; Wang, Lan; Liu, Wei; Xu, Fei; Wu, Pin; Wang, Yuhao; Chen, Shujie; Wang, Liangjing.
Afiliação
  • Jia D; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Wang Q; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Qi Y; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Jiang Y; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • He J; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Lin Y; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Sun Y; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Xu J; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Chen W; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Fan L; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Yan R; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Zhang W; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Ren G; Department of Breast Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
  • Xu C; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Ge Q; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Wang L; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
  • Liu W; Institute of Plant Protection and Microbiology, Zhejiang Academy of Agriculture Sciences, Hangzhou, Zhejiang Province 310021, China.
  • Xu F; Institute of Pharmaceutical Biotechnology and Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
  • Wu P; Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
  • Wang Y; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
  • Chen S; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province 310001, China. E
  • Wang L; Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang Pro
Cell ; 187(7): 1651-1665.e21, 2024 Mar 28.
Article em En | MEDLINE | ID: mdl-38490195
ABSTRACT
The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD8-Positivos / Imunoterapia / Lactobacillus / Neoplasias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD8-Positivos / Imunoterapia / Lactobacillus / Neoplasias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China