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Mechanistically, tumor-derived TGF-\u03b21 activated CAFs via SMAD signaling, inducing POSTN and recruiting APOE\n                    <jats:sup>+<\/jats:sup>\n                    TAMs through integrin and chemokine axes. TAMs secreted TGF-\u03b21 and VEGFA, amplifying stromal programs and sustaining exclusion. Blocking POSTN reprogrammed macrophages, reduced matrix-mediated suppression, and restored CD8\n                    <jats:sup>+<\/jats:sup>\n                    infiltration. In vivo, POSTN inhibition combined with ICB boosted antitumor immunity, reduced tumor burden, and reversed immunosuppressive infiltration, nominating POSTN-directed strategies to potentiate ICB.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed0733","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:59:18Z","timestamp":1786125558000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["APOE\n                    <sup>+<\/sup>\n                    macrophages and POSTN\n                    <sup>+<\/sup>\n                    CAFs form immune-exclusion niche driving immunotherapy resistance in clear-cell renal carcinoma"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-6699","authenticated-orcid":true,"given":"Qintao","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Urology, Fudan University Shanghai Cancer Center; Department of Oncology,\u00a0Shanghai\u00a0Medical\u00a0College; Qingdao Institute of Life Sciences, Fudan University, Shanghai, 200032, P.R. 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