Seif Farhad, Torki Zahra, Zalpoor Hamidreza, Habibi Mehran, Pornour Majid
Department of Immunology and Allergy, Academic Center for Education, Culture (ACECR), and Research (ACECR), Tehran, Iran.
Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran.
Mol Ther Oncolytics. 2023 Jan 11;28:132-157. doi: 10.1016/j.omto.2023.01.001. eCollection 2023 Mar 16.
The tumor microenvironment (TME) comprises a variety of immune cells, among which T cells exert a prominent axial role in tumor development or anti-tumor responses in patients with breast cancer (BC). High or low levels of anti-inflammatory cytokines, such as transforming growth factor β, in the absence or presence of proinflammatory cytokines, such as interleukin-6 (IL-6), delineate the fate of T cells toward either regulatory T (Treg) or T helper 17 (Th17) cells, respectively. The transitional state of RORγtFoxp3 Treg (IL-17-producing Treg) resides in the middle of this reciprocal polarization, which is known as Treg/IL-17-producing Treg/Th17 cell axis. TME secretome, including microRNAs, cytokines, and extracellular vesicles, can significantly affect this axis. Furthermore, immune checkpoint inhibitors may be used to reconstruct immune cells; however, some of these novel therapies may favor tumor development. Therefore, understanding secretory and cell-associated factors involved in their differentiation or polarization and functions may be targeted for BC management. This review discusses microRNAs, cytokines, and extracellular vesicles (as secretome), as well as transcription factors and immune checkpoints (as cell-associated factors), which influence the Treg/IL-17-producing Treg/Th17 cell axis in BC. Furthermore, approved or ongoing clinical trials related to the modulation of this axis in the TME of BC are described to broaden new horizons of promising therapeutic approaches.
肿瘤微环境（TME）由多种免疫细胞组成，其中T细胞在乳腺癌（BC）患者的肿瘤发展或抗肿瘤反应中发挥着重要的轴心作用。在存在或不存在促炎细胞因子（如白细胞介素-6（IL-6））的情况下，抗炎细胞因子（如转化生长因子β）的高或低水平分别决定了T细胞向调节性T（Treg）细胞或辅助性T 17（Th17）细胞的分化命运。RORγtFoxp3 Treg（产生IL-17的Treg）的过渡状态处于这种相互极化的中间，这被称为Treg/产生IL-17的Treg/Th17细胞轴。TME分泌组，包括微小RNA、细胞因子和细胞外囊泡，可显著影响该轴。此外，免疫检查点抑制剂可用于重建免疫细胞；然而，其中一些新疗法可能有利于肿瘤发展。因此，了解参与其分化、极化和功能的分泌性和细胞相关因子可能成为BC治疗的靶点。本综述讨论了微小RNA、细胞因子和细胞外囊泡（作为分泌组），以及转录因子和免疫检查点（作为细胞相关因子），它们在BC中影响Treg/产生IL-17的Treg/Th17细胞轴。此外，还描述了与调节BC的TME中该轴相关的已批准或正在进行的临床试验，以拓宽有前景的治疗方法的新视野。
