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Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.
Lu, Jia-Cheng; Wu, Lei-Lei; Sun, Yi-Ning; Huang, Xiao-Yong; Gao, Chao; Guo, Xiao-Jun; Zeng, Hai-Ying; Qu, Xu-Dong; Chen, Yi; Wu, Dong; Pei, Yan-Zi; Meng, Xian-Long; Zheng, Yi-Min; Liang, Chen; Zhang, Peng-Fei; Cai, Jia-Bin; Ding, Zhen-Bin; Yang, Guo-Huan; Ren, Ning; Huang, Cheng; Wang, Xiao-Ying; Gao, Qiang; Sun, Qi-Man; Shi, Ying-Hong; Qiu, Shuang-Jian; Ke, Ai-Wu; Shi, Guo-Ming; Zhou, Jian; Sun, Yi-Di; Fan, Jia.
Afiliación
  • Lu JC; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Wu LL; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Sun YN; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Huang XY; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Gao C; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Guo XJ; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Zeng HY; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Qu XD; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Chen Y; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Wu D; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Pei YZ; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Meng XL; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Zheng YM; Department of Intervention Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Liang C; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Zhang PF; Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Cai JB; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Ding ZB; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Yang GH; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Ren N; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Huang C; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Wang XY; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Gao Q; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Sun QM; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Shi YH; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Qiu SJ; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Ke AW; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
  • Shi GM; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Zhou J; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education of the People's Republic of China, Shanghai, 200032, China.
  • Sun YD; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Fan J; Liver cancer Institute, Fudan University, Shanghai, 200032, China.
Nat Commun ; 15(1): 621, 2024 Jan 20.
Article en En | MEDLINE | ID: mdl-38245530
ABSTRACT
Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Quinolinas / Neoplasias de los Conductos Biliares / Colangiocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Quinolinas / Neoplasias de los Conductos Biliares / Colangiocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China