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Global and myeloid\u2010specific\n                      <jats:italic>Cxcr2<\/jats:italic>\n                      knockout models, in vitro co\u2010cultures (macrophages, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and tumor cells), and patient\u2010derived organoid (PDO) systems were employed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DESMIN\n                      <jats:sup>+<\/jats:sup>\n                      CAFs were the predominant source of IL\u20108 and promoted tumorigenesis and M2\u2010like macrophage accumulation via the IL\u20108\/CXCR2 axis. Genetic deletion of\n                      <jats:italic>Cxcr2<\/jats:italic>\n                      , myeloid\u2010specific knockout, or pharmacological blockade reduced M2\u2010like macrophage polarization through the PI3K\/AKT\/RhoA\/MRTF\u2010A\/SRF pathway, restored CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell effector function, and suppressed tumor progression. CXCR2 blockade also synergized with chemotherapy and anti\u2010PD\u2010L1 immunotherapy in murine models. In human PDO co\u2010cultures with matched DESMIN\n                      <jats:sup>+<\/jats:sup>\n                      CAFs and autologous CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, CXCR2 inhibition attenuated M2\u2010like polarization and enhanced T cell\u2010mediated killing of tumor organoids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      DESMIN\n                      <jats:sup>+<\/jats:sup>\n                      CAFs drive an immunosuppressive tumor microenvironment in LC through IL\u20108\/CXCR2 signaling and downstream MRTF\u2010A activation. Targeting this axis represents a promising strategy to overcome treatment resistance in LC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/advs.202508001","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:34:27Z","timestamp":1784198067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stromal\u2010Derived IL\u20108 Promotes M2 Macrophage Polarization via the RhoA\/MRTF\u2010A\/SRF Transcriptional Axis to Impair CD8\n                    <sup>+<\/sup>\n                    T Cell Cytotoxicity in Lung Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Xuyu","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Oncology School of Medicine Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University  Shanghai 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