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Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.
Chen, Jian; Zhao, Deping; Wang, Yupeng; Liu, Ming; Zhang, Yuan; Feng, Tingting; Xiao, Chao; Song, Huan; Miao, Rui; Xu, Li; Chen, Hongwei; Qiu, Xiaoying; Xu, Yi; Xu, Jingxuan; Cui, Zelin; Wang, Wei; Quan, Yanchun; Zhu, Yifeng; Huang, Chen; Zheng, Song Guo; Zhao, Jian-Yuan; Zhu, Ting; Sun, Lianhui; Fan, Guangjian.
Afiliación
  • Chen J; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Zhao D; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, 200433, P. R. China.
  • Wang Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, 200433, P. R. China.
  • Liu M; Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, P. R. China.
  • Zhang Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, 200433, P. R. China.
  • Feng T; Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Xiao C; Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Song H; Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200040, P. R. China.
  • Miao R; Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, P. R. China.
  • Xu L; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Chen H; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, 200433, P. R. China.
  • Qiu X; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Xu Y; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Xu J; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Cui Z; Institute of Transfusion Medicine and Immunology, Mannheim Institute of Innate Immunosciences (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
  • Wang W; Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Quan Y; Department of Breast-thyroid Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Zhu Y; Central Laboratory, Linyi People's Hospital, Shandong, 273300, P. R. China.
  • Huang C; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
  • Zheng SG; Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Zhao JY; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
  • Zhu T; Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, P. R. China.
  • Sun L; Department of Immunology, School of Cell and Gene Therapy, Songjiang Research Institute, Shanghai Jiaotong University School of Medicine Affiliated Songjiang Hospital, Shanghai, 200080, P. R. China.
  • Fan G; Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
Adv Sci (Weinh) ; : e2406333, 2024 Jul 09.
Article en En | MEDLINE | ID: mdl-38981044
ABSTRACT
Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article Pais de publicación: Alemania