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Brentuximab vedotin (BV), a CD30\u2010targeting antigen\u2010drug conjugate approved for CD30\n                    <jats:sup>+<\/jats:sup>\n                    MF following prior systemic treatment, still exhibits resistance with unclarified mechanisms. With single\u2010cell RNA analysis on 13 paired tumor samples from 6 CD30\n                    <jats:sup>+<\/jats:sup>\n                    MF patients, we revealed that BV\u2010induced immunogenic cell death (ICD) in both CD30\n                    <jats:sup>+<\/jats:sup>\n                    and CD30\n                    <jats:sup>\u2212<\/jats:sup>\n                    malignant T cells while specifically enhanced interferon\u2010\u03b1 (IFN\u03b1) and IFN\u03b3 responses in CD30\n                    <jats:sup>\u2212<\/jats:sup>\n                    subsets. BV also directly targeted CD30\n                    <jats:sup>+<\/jats:sup>\n                    tumor\u2010infiltrating regulatory T cells (TI\u2010Tregs), and activated anti\u2010tumor immunity mediated by dendritic cells and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The treatment responses and mechanistic insights were validated using seven CTCL cell lines. Resistance arose from upregulated drug efflux transporters and impaired endosomal processing in CD30\n                    <jats:sup>+<\/jats:sup>\n                    malignant T cells, while CD30\n                    <jats:sup>\u2212<\/jats:sup>\n                    tumor cells showed blunted IFN\u03b1 and IFN\u03b3 responses. Anti\u2010apoptotic BCL2 was upregulated in all tumor cells from nonresponsive lesions, especially in CD30\n                    <jats:sup>\u2212<\/jats:sup>\n                    subsets. We further confirmed a potent synergy between BV and BCL2 inhibitors in tumor cell lines, indicating a promising strategy to overcome resistance in CTCL.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517353","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:05:46Z","timestamp":1772993146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond CD30: Dual\u2010Targeting of Malignant and Regulatory T Cells by Brentuximab Vedotin Remodels the Lymphoma Microenvironment and Overcomes Resistance via BCL2 Inhibition in Mycosis Fungoides"],"prefix":"10.1002","volume":"13","author":[{"given":"Yi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology Peking University First Hospital  Beijing China"},{"name":"National Clinical Research Center for Skin and Immune Diseases  Beijing China"},{"name":"NMPA Key Laboratory for Quality 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