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Shaping immune landscape of colorectal cancer by cholesterol metabolites.
Bai, Yibing; Li, Tongzhou; Wang, Qinshu; You, Weiqiang; Yang, Haochen; Xu, Xintian; Li, Ziyi; Zhang, Yu; Yan, Chengsong; Yang, Lei; Qiu, Jiaqian; Liu, Yuanhua; Chen, Shiyang; Wang, Dongfang; Huang, Binlu; Liu, Kexin; Song, Bao- Liang; Wang, Zhuozhong; Li, Kang; Liu, Xin; Wang, Guangchuan; Yang, Weiwei; Chen, Jianfeng; Hao, Pei; Zhang, Zemin; Wang, Zhigang; Zhu, Zheng-Jiang; Xu, Chenqi.
Afiliación
  • Bai Y; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Li T; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Wang Q; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • You W; Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Yang H; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Xu X; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China.
  • Li Z; Beijing Advanced Innovation Center for Genomics, BIOPIC and School of Life Sciences, Peking University, Beijing, China.
  • Zhang Y; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Yan C; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Yang L; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Qiu J; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Liu Y; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China.
  • Chen S; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Wang D; Beijing Advanced Innovation Center for Genomics, BIOPIC and School of Life Sciences, Peking University, Beijing, China.
  • Huang B; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Liu K; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Song BL; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
  • Wang Z; The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Li K; Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, China.
  • Liu X; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Wang G; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Yang W; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Chen J; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Hao P; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China.
  • Zhang Z; Beijing Advanced Innovation Center for Genomics, BIOPIC and School of Life Sciences, Peking University, Beijing, China.
  • Wang Z; Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. wangzhigang72@sjtu.edu.cn.
  • Zhu ZJ; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. jiangzhu@sioc.ac.cn.
  • Xu C; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. cqxu@sibcb.ac.cn.
EMBO Mol Med ; 16(2): 334-360, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38177537
ABSTRACT
Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Inestabilidad de Microsatélites Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Inestabilidad de Microsatélites Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article