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It is first identified that iRFA\u2010treated tumors exhibited increased pyruvate kinase M2 (PKM2) expression, exacerbated tumor immunosuppression featured with increased tumor infiltration of suppressive immune cells and increased proliferation, and programmed cell death ligand 1 expression of cancer cell and ultimately a poor prognosis. Herein, a multifunctional nanomedicine is fabricated by encapsulating nanoassemblies of anti\u2010PD\u2010L1 and spermidine\u2010grafted oxidized dextran with shikonin\u2010containing lipid bilayers to reverse iRFA\u2010induced treatment failure. Shikonin, a PKM2 inhibitor, is used to suppress glycolysis in cancer cells, while anti\u2010PD\u2010L1 and spermidine are introduced to collectively reprogram the proliferation and functions of infiltrated CD8+ T lymphocytes. Combined with iRFA, which promoted the exposure of tumor antigens, the intravenous injection of liposomal SPS\u2010NPs effectively stimulated dendritic cell maturation and reversed tumor immunosuppression, thus eliciting potent antitumor immunity to synergistically suppress the growth of residual tumor masses and lung metastasis. The as\u2010prepared liposomal nanomedicine is promising for potentiating the therapeutic benefits of RFA toward advanced HCC patients through reprogramming iRFA\u2010induced tumor immunosuppression.<\/jats:p>","DOI":"10.1002\/adhm.202403979","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T01:26:21Z","timestamp":1739841981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tailored Liposomal Nanomedicine Suppresses Incomplete Radiofrequency Ablation\u2010Induced Tumor Relapse by Reprogramming Antitumor Immunity"],"prefix":"10.1002","volume":"14","author":[{"given":"Duo","family":"Wang","sequence":"first","affiliation":[{"name":"Center of Interventional Radiology &amp; Vascular Surgery Department of Radiology Zhongda Hospital Medical School Southeast University  Nanjing 224001 China"},{"name":"Basic Medicine Research and Innovation Center of Ministry of Education Zhongda 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