尽管免疫系统在检测和消除异常细胞方面发挥着重要作用，但癌细胞常常通过利用各种免疫逃逸机制来逃避消除。这些机制之一是癌细胞上调氨基酸代谢酶或在肿瘤浸润免疫抑制细胞中诱导这些酶的能力。氨基酸是多种生理过程所需的基本细胞营养素，其不足会严重影响免疫细胞功能。氨基酸衍生的代谢物还可以通过其免疫抑制活性来抑制抗肿瘤免疫反应，同时有些还可以直接促进肿瘤生长。基于它们在肿瘤免疫逃逸中的明显作用，氨基酸代谢酶谷氨酰胺酶 1 (GLS1)、精氨酸酶 1 (ARG1)、诱导型一氧化氮合酶 (iNOS)、吲哚胺 2,3-双加氧酶 1 (IDO1)、色氨酸 2、 3-双加氧酶 (TDO) 和白细胞介素 4 诱导 1 (IL4I1) 均是免疫治疗干预的有希望的靶标。本综述总结并讨论了这些酶在癌症中的作用、它们对抗肿瘤免疫反应的影响以及针对这些酶的抑制剂的临床前和临床评估的最新进展。版权所有 © 2024 Grobben。

Despite the immune system's role in the detection and eradication of abnormal cells, cancer cells often evade elimination by exploitation of various immune escape mechanisms. Among these mechanisms is the ability of cancer cells to upregulate amino acid-metabolizing enzymes, or to induce these enzymes in tumor-infiltrating immunosuppressive cells. Amino acids are fundamental cellular nutrients required for a variety of physiological processes, and their inadequacy can severely impact immune cell function. Amino acid-derived metabolites can additionally dampen the anti-tumor immune response by means of their immunosuppressive activities, whilst some can also promote tumor growth directly. Based on their evident role in tumor immune escape, the amino acid-metabolizing enzymes glutaminase 1 (GLS1), arginase 1 (ARG1), inducible nitric oxide synthase (iNOS), indoleamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase (TDO) and interleukin 4 induced 1 (IL4I1) each serve as a promising target for immunotherapeutic intervention. This review summarizes and discusses the involvement of these enzymes in cancer, their effect on the anti-tumor immune response and the recent progress made in the preclinical and clinical evaluation of inhibitors targeting these enzymes.Copyright © 2024 Grobben.