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Radiotherapy (RT) is a cornerstone of TNBC treatment; however, preclinical studies suggest that RT may both stimulate and suppress immune responses within the tumor microenvironment (TME). While RT can enhance immune responses, it may also induce an immunosuppressive TME, contributing to radioresistance. The renin\u2010angiotensin system (RAS) is also involved in the immunosuppressive TME and tumor radioresistance. Previous research showed blocker of angiotensin II receptor (AGTR1), losartan, as a RAS inhibitor, could alleviate hypoxia, thereby enhancing RT efficacy. Our study shows that high levels of AGTR1 may confer a poor prognosis and radioresistance in TNBC, and innovatively demonstrates losartan could enhance the radiosensitivity of TNBC in an immune dependent way. Furthermore, we found losartan could inhibit tumor\u2010associated macrophages (TAMs) polarizing towards M2 phenotype, impedes the immunosuppressive function of myeloid\u2010derived suppressive cells (MDSCs) induced by RT, and ultimately up\u2010regulates the number and function of tumor\u2010infiltrating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes. Besides, RNA\u2010seq data reveals losartan impedes JAK2\/STAT1 signaling activation upon irradiation, suppresses the interferon\u2010related DNA damage resistant signature (IRDS) expression and diminishes the immune suppressive factors PD\u2010L1 and IDO induced by irradiation in TNBC cells. Collectively, in our study, we investigate the role of losartan in radiosensitization and demonstrate losartan could reverse the immunosuppressive TME induced by RT in TNBC, which suggests that losartan combined with RT may represent a promising strategy for the treatment of TNBC.\n                  <\/jats:p>","DOI":"10.1111\/cas.70407","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:05:56Z","timestamp":1778159156000},"page":"1795-1812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in\n                    <scp>TNBC<\/scp>"],"prefix":"10.1111","volume":"117","author":[{"given":"Xu","family":"Wang","sequence":"first","affiliation":[{"name":"Cancer Center, Union Hospital Tongji Medical College, Huazhong University of Science and Technology  Wuhan 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