靶向酰基辅酶A合成酶长链家族以调节铁死亡和癌症免疫。

Targeting ACSLs to modulate ferroptosis and cancer immunity.

作者信息

Lin Junhong, Lai Yongfeng, Lu Fujia, Wang Weimin

机构信息

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.

Department of Breast Disease Comprehensive Center, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

出版信息

Trends Endocrinol Metab. 2024 Oct 17. doi: 10.1016/j.tem.2024.09.003.

DOI:10.1016/j.tem.2024.09.003

PMID:39424456

Abstract

Five acyl-CoA synthetase long-chain family members (ACSLs) are responsible for catalyzing diverse long-chain fatty acids (LCFAs) into LCFA-acyl-coenzyme A (CoA) for their subsequent metabolism, including fatty acid oxidation (FAO), lipid synthesis, and protein acylation. In this review, we focus on ACSLs and their LCFA substrates and introduce their involvement in regulation of cancer proliferation, metastasis, and therapeutic resistance. Along with the recognition of the decisive role of ACSL4 in ferroptosis - an immunogenic cell death (ICD) initiated by lipid peroxidation - we review the functions of ACSLs on regulating ferroptosis sensitivity. Last, we discuss the current understanding of ACSL on the antitumor immune response. We emphasize the necessity to explore the functions of immune cells expressing ACSLs for developing novel strategies to augment immunotherapy by targeting ACSL.

摘要

五种酰基辅酶A合成酶长链家族成员（ACSLs）负责催化多种长链脂肪酸（LCFAs）生成LCFA-酰基辅酶A（CoA），以供后续代谢，包括脂肪酸氧化（FAO）、脂质合成和蛋白质酰化。在本综述中，我们聚焦于ACSLs及其LCFA底物，并介绍它们在调节癌症增殖、转移和治疗耐药性中的作用。随着对ACSL4在铁死亡（一种由脂质过氧化引发的免疫原性细胞死亡（ICD））中决定性作用的认识，我们综述了ACSLs在调节铁死亡敏感性方面的功能。最后，我们讨论了目前对ACSLs在抗肿瘤免疫反应方面的理解。我们强调，为了开发通过靶向ACSLs增强免疫治疗的新策略，探索表达ACSLs的免疫细胞功能的必要性。