Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Mol Biol Rep. 2023 Jul;50(7):6133-6145. doi: 10.1007/s11033-023-08469-3. Epub 2023 May 22.
Indoleamine-2,3 dioxygenase is a rate-limiting enzyme in the tryptophan catabolism in kynurenine pathways that has an immunosuppressive effect and supports cancer cells to evade the immune system in different cancer types. Diverse cytokines and pathways upregulate the production of indoleamine-2,3 dioxygenase enzymes in the tumor microenvironment and cause more production and activity of this enzyme. Ultimately, this situation results in anti-tumor immune suppression which is in favor of tumor growth. Several inhibitors such as 1-methyl-tryptophan have been introduced for indoleamine-2,3 dioxygenase enzyme and some of them are widely utilized in pre-clinical and clinical trials. Importantly at the molecular level, indoleamine-2,3 dioxygenase is positioned in a series of intricate signaling and molecular networks. Here, the main objective is to provide a focused view of indoleamine-2,3 dioxygenase enhancer pathways and propose further studies to cover the gap in available information on the function of indoleamine-2,3 dioxygenase enzyme in the tumor microenvironment.
色氨酸-2,3 双加氧酶是犬尿氨酸途径中色氨酸分解的限速酶，具有免疫抑制作用，并支持不同类型的癌症细胞逃避免疫系统。多种细胞因子和途径上调肿瘤微环境中色氨酸-2,3 双加氧酶的产生，并导致这种酶的更多产生和活性。最终，这种情况导致抗肿瘤免疫抑制，有利于肿瘤生长。已经引入了几种色氨酸-2,3 双加氧酶抑制剂，如 1-甲基色氨酸，其中一些已广泛用于临床前和临床试验。重要的是，在分子水平上，色氨酸-2,3 双加氧酶位于一系列复杂的信号和分子网络中。在这里，主要目的是提供对色氨酸-2,3 双加氧酶增强途径的重点观察，并提出进一步的研究来填补肿瘤微环境中色氨酸-2,3 双加氧酶功能信息的空白。
