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Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila.
Zhu, Zhuxian; Huang, Jianguo; Zhang, Yanling; Hou, Weiwei; Chen, Fei; Mo, Yin-Yuan; Zhang, Ziqiang.
Afiliación
  • Zhu Z; Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
  • Huang J; Earle A. Chiles Research Institute, a division of Providence Cancer Institute, Portland, OR 97213, USA.
  • Zhang Y; Department of Emergency Medicine, Tongji University School of Medicine, Shanghai 200065, China.
  • Hou W; Department of Clinical Laboratory, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
  • Chen F; Department of Emergency Medicine, Tongji University School of Medicine, Shanghai 200065, China.
  • Mo YY; Institute of Clinical Medicine, Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou 310014 , China. Electronic address: moyinyuan@hmc.edu.cn.
  • Zhang Z; Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong Hospital of Fudan University, Shanghai 201399, China. Electronic address: zzq1419@126.com.
Cell Rep ; 43(6): 114306, 2024 Jun 25.
Article en En | MEDLINE | ID: mdl-38819989
ABSTRACT
Gut Akkermansia muciniphila (Akk) has been implicated in impacting immunotherapy or oncogenesis. This study aims to dissect the Akk-associated tumor immune ecosystem (TIME) by single-cell profiling coupled with T cell receptor (TCR) sequencing. We adopted mouse cancer models under anti-PD-1 immunotherapy, combined with oral administration of three forms of Akk, including live Akk, pasteurized Akk (Akk-past), or its membrane protein Amuc_1100 (Amuc). We show that live Akk is most effective in activation of CD8 T cells by rescuing the exhausted type into cytotoxic subpopulations. Remarkably, only live Akk activates MHC-II-pDC pathways, downregulates CXCL3 in Bgn(+)Dcn(+) cancer-associated fibroblasts (CAFs), blunts crosstalk between Bgn(+)Dcn(+) CAFs and PD-L1(+) neutrophils by a CXCL3-PD-L1 axis, and further suppresses the crosstalk between PD-L1(+) neutrophils and CD8 T cells, leading to the rescue of exhausted CD8 T cells. Together, this comprehensive picture of the tumor ecosystem provides deeper insights into immune mechanisms associated with gut Akk-dependent anti-PD-1 immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Receptor de Muerte Celular Programada 1 / Akkermansia / Inmunoterapia / Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Receptor de Muerte Celular Programada 1 / Akkermansia / Inmunoterapia / Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos