Targeting ACSLs to modulate ferroptosis and cancer immunity.

Trends Endocrinol Metab

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; 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; Cell Architecture Research Institute, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Published: October 2024

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.

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http://dx.doi.org/10.1016/j.tem.2024.09.003DOI Listing

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