{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:06:50Z","timestamp":1779944810901,"version":"3.53.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options. Reprogramming the tumor immune microenvironment (TIME) has emerged as a promising strategy for breast cancer treatment, and tumor-associated macrophages, the most abundant and heterogeneous immune cells in the solid TIME, play a pivotal role in this process. This study aimed to investigate the TNBC-specific TIME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Multiplex fluorescence immunohistochemistry and bioinformatic analyses were employed to map the immune landscape and predict potential regulatory mechanisms. These predictions were subsequently validated using\n                      <jats:italic>in vitro<\/jats:italic>\n                      cellular assays and\n                      <jats:italic>in vivo<\/jats:italic>\n                      mouse models. The unique lipid metabolic signature of TNBC was integrated with its distinct immune contexture to identify key regulators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The oxysterol metabolite 25-hydroxycholesterol (25HC) was identified as a key regulator of macrophage polarization. Specifically, we discovered that an aberrantly activated interferon regulatory factor 7\u2013cholesterol-25-hydroxylase\u201325HC axis in TNBC cells potently inhibits CD163\n                      <jats:sup>+<\/jats:sup>\n                      macrophage polarization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>To our knowledge, this is the first study to delineate the link between dysregulated 25HC metabolism within the TIME and the control of macrophage polarization. These findings provide novel insights into the immunometabolic mechanisms underlying TNBC aggressiveness and reveal a potential therapeutic target for this devastating disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1812056","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:44:15Z","timestamp":1779943455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["25HC regulates the polarization of CD163+ macrophages in the immune microenvironment of triple-negative breast cancer through the interferon pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongmei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Breast Center, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan Clinical Research Center for Breast 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