{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:57:24Z","timestamp":1791201444923,"version":"4.2.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Malignant pleural effusion (MPE) correlates with poor prognosis. Tumor-associated macrophages dominate the immune microenvironment and govern MPE progression, while the functional heterogeneity of macrophage subsets in MPE remains poorly understood. CD169\n                      <jats:sup>+<\/jats:sup>\n                      macrophages exhibit context-dependent tumor-regulatory functions in various malignancies, yet their phenotypic characteristics and biological roles in MPE remain uncharacterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CD169\u207a macrophages and their CD169\n                      <jats:sup>low<\/jats:sup>\n                      small and CD169\n                      <jats:sup>high<\/jats:sup>\n                      large subsets were characterized in PPE, IPE, and lung adenocarcinoma-associated MPE, as well as in a murine MPE model, by flow cytometry. Their associations with MPE control were analyzed. The effects of CXCL2\/CXCR2 signaling on macrophage migration, proliferation, and apoptosis were evaluated using recombinant human CXCL2 and the CXCR2 inhibitor SB225002\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and the therapeutic effects of CXCR2 inhibition were assessed\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CD169\u207a macrophages, including CD169\n                      <jats:sup>low<\/jats:sup>\n                      small and CD169\n                      <jats:sup>high<\/jats:sup>\n                      large macrophages, were significantly enriched in lung adenocarcinoma-associated MPE (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). Only CD169\n                      <jats:sup>high<\/jats:sup>\n                      large macrophages were negatively associated with MPE control (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05) and exhibited an immunosuppressive phenotype. Macrophages were the predominant CXCL2-expressing population in single-cell analysis. CXCL2 promoted macrophage migration, whereas CXCR2 inhibition with SB225002 attenuated this effect without affecting macrophage proliferation or apoptosis.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , SB225002 reduced pleural effusion volume, CD169\n                      <jats:sup>high<\/jats:sup>\n                      macrophage accumulation, and tumor burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We identified a distinct population of CD169\n                      <jats:sup>high<\/jats:sup>\n                      large macrophages that is enriched in lung adenocarcinoma-associated MPE and exhibits an immunosuppressive phenotype. CXCL2\/CXCR2 axis promotes macrophage migration and contributes to the accumulation of CD169\n                      <jats:sup>high<\/jats:sup>\n                      macrophages in the MPE microenvironment, thereby facilitating MPE progression. These findings provide new insights into the myeloid-cell regulatory mechanisms underlying MPE and may represent a potential therapeutic strategy for lung cancer-associated MPE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1943314","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:16:23Z","timestamp":1788948983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCL2\/CXCR2 pathway regulates CD169high large macrophages to promote progression of malignant pleural effusion from lung adenocarcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Sitong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Zhoushan Hospital, Wenzhou Medical University","place":["Zhoushan, Zhejiang, China"]},{"name":"Cellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical 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