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Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Lai Yongfeng[1] * ; Gao Yuan[2] * ; Lin Junhong[1] ; Liu Fangfang[2] ; Yang Liguo[1] ; Zhou Jie[1] ; Xue Ying[1] ; Li Yan[1] ; Chang Zhenzhen[1] ; Li Jing[1] ; Chao Tengfei[2] ; Chen Jing[3] ; Cheng Xiang[4] ; Gao Xianfu[5] ; Li Xiong[6] ; Lu Fujia[1] ; Chu Qian[2] ; Wang Weimin[1,7,8] ;
单位： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China [2]Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [3]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [4]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [5]Shanghai ProfLeader Biotech Co., Ltd, Shanghai, China [6]Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [7]Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China [8]Cell Architecture Research Institute, Huazhong University of Science and Technology, Wuhan, China
出处：
DOI： 10.1016/j.cmet.2024.01.012
ISSN：

摘要：
Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.Copyright © 2024 Elsevier Inc. All rights reserved.

基金：
This work was supported in part by grants from the National Key R&D Program of China (grant 2021YFC2400600/2021YFC2400602); the National Natural Science Foundation of China to W.W. (grants 81902930 and 82073177), F.L. (grant 82102930), and Q.C. (grants 82072597 and 62131009); the Natural Science Foundation of Hubei Province to W.W. (grant 2022CFA056); and the Independent Innovation Grant from Huazhong University of Science & Technology to W.W. (grant 2021GCRC072).
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外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
JCR分区：
出版当年[2022]版：
Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM
最新[2023]版：
Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China [7]Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China [8]Cell Architecture Research Institute, Huazhong University of Science and Technology, Wuhan, China
推荐引用方式(GB/T 7714)：
Lai Yongfeng,Gao Yuan,Lin Junhong,et al.Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5[J].Cell Metabolism.2024,doi:10.1016/j.cmet.2024.01.012.
APA：
Lai Yongfeng,Gao Yuan,Lin Junhong,Liu Fangfang,Yang Liguo...&Wang Weimin.(2024).Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.Cell Metabolism,,
MLA：
Lai Yongfeng,et al."Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5".Cell Metabolism .(2024)

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