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.

中文翻译：

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靶向 ACSL 以调节铁死亡和癌症免疫。


五个酰基辅酶 A 合成酶长链家族成员 （ACSL） 负责催化多种长链脂肪酸 （LCFA） 转化为 LCFA-酰基辅酶 A （CoA） 进行后续代谢，包括脂肪酸氧化 （FAO）、脂质合成和蛋白质酰化。在这篇综述中，我们重点介绍了 ACSLs 及其 LCFA 底物，并介绍了它们在调节癌症增殖、转移和治疗耐药性中的参与。随着认识到 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））中的决定性作用，我们回顾了 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 ACSL 对抗肿瘤免疫反应的理解。我们强调探索表达 ACSLs 的免疫细胞功能的必要性，以开发通过靶向 ACSL 来增强免疫治疗的新策略。