{"title":"Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives.","authors":"Farhad Seif, Zahra Torki, Hamidreza Zalpoor, Mehran Habibi, Majid Pornour","doi":"10.1016/j.omto.2023.01.001","DOIUrl":null,"url":null,"abstract":"<p><p>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 RORγt<sup>+</sup>Foxp3<sup>+</sup> 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.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"132-157"},"PeriodicalIF":5.3000,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922830/pdf/","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy Oncolytics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omto.2023.01.001","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 10
Abstract
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 RORγt+Foxp3+ 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.
期刊介绍:
Molecular Therapy — Oncolytics is an international, online-only, open access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer.