Sarangi Pratyasha
School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha 751024, India.
Cancer Pathog Ther. 2023 Nov 7;2(4):246-255. doi: 10.1016/j.cpt.2023.11.001. eCollection 2024 Oct.
Breast cancer (BC) contributes greatly to global cancer incidence and is the main cause of cancer-related deaths among women globally. It is a complex disease characterized by numerous subtypes with distinct clinical manifestations. Immune checkpoint inhibitors (ICIs) are not effective in all patients and have been associated with tumor resistance and immunosuppression. Because amino acid (AA)-catabolizing enzymes have been shown to regulate immunosuppressive effects, this review investigated the immunosuppressive roles of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme, which is overexpressed in various metastatic tumors. It promotes immunomodulatory effects by depleting Trp in the regional microenvironment. This leads to a reduction in the number of immunogenic immune cells, such as effector T and natural killer (NK) cells, and an increase in tolerogenic immune cells, such as regulatory T (Treg) cells. The BC tumor microenvironment (TME) establishes a supportive niche where cancer cells can interact with immune cells and neighboring endothelial cells and is thus a feasible target for cancer therapy. In many immunological contexts, IDO1 regulates immune control by causing regional metabolic changes in the TME and tissue environment, which may further affect the maturation of systemic immunological tolerance. In the development of effective treatment targets and approaches, it is essential to understand the immunomodulatory effects exerted by AA-catabolizing enzymes, such as IDO1, on the components of the TME.
乳腺癌（BC）在全球癌症发病率中占比极大，是全球女性癌症相关死亡的主要原因。它是一种复杂的疾病，具有多种具有不同临床表现的亚型。免疫检查点抑制剂（ICI）并非对所有患者都有效，且与肿瘤耐药性和免疫抑制有关。由于氨基酸（AA）分解代谢酶已被证明可调节免疫抑制作用，本综述研究了色氨酸（Trp）分解代谢酶吲哚胺2,3-双加氧酶1（IDO1）的免疫抑制作用，该酶在各种转移性肿瘤中均有过表达。它通过消耗局部微环境中的色氨酸来促进免疫调节作用。这导致免疫原性免疫细胞数量减少，如效应T细胞和自然杀伤（NK）细胞，而耐受性免疫细胞数量增加，如调节性T（Treg）细胞。乳腺癌肿瘤微环境（TME）建立了一个支持性生态位，癌细胞可在此与免疫细胞和邻近内皮细胞相互作用，因此是癌症治疗的一个可行靶点。在许多免疫背景下，IDO1通过引起TME和组织环境中的局部代谢变化来调节免疫控制，这可能会进一步影响全身免疫耐受的成熟。在开发有效的治疗靶点和方法时，了解诸如IDO1等AA分解代谢酶对TME成分所发挥的免疫调节作用至关重要。
