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Regulating cellular metabolism represents a promising strategy to enhance cancer immunotherapy; however, redirecting glucose utilization from tumor cells to T cells is challenging. Herein, the activation of cytotoxic T cells using engineered peptide coacervates (PCs) containing interferon alpha (IFN\u03b1) and membranized with metal\u2013phenolic networks (MPNs) (PC\u2010IFN\u03b1@MPNs), which promote glucose uptake and glycolysis, is reported. PC\u2010IFN\u03b1@MPNs modulate the molecular conformation of the co\u2010stimulatory lymphocyte function\u2010associated antigen 1 on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, while suppressing tumor cell glycolysis through the sustained release of IFN\u03b1, thereby increasing the energy supply for T cells. Furthermore, PC\u2010IFN\u03b1@MPNs suppress tumor progression in preclinical orthotopic tumor mouse models by facilitating T cell infiltration and activation. When combined with immune checkpoint blockade (ICB), PC\u2010IFN\u03b1@MPNs further improve therapeutic outcomes (99% inhibition of tumor growth), even in ICB\u2010insensitive tumor models. Notably, PC\u2010IFN\u03b1@MPNs exert a robust immune\u2010memory effect (a 4.8\u2010fold increase in memory T cells) and provide long\u2010lasting anti\u2010tumor activity (over 74 days), thereby preventing postsurgical tumor recurrence. The present study offers insights into metabolic intervention mechanisms mediated by glucose modulation and provides a rational design for metal\u2013organic materials in cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202510936","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T11:22:12Z","timestamp":1756898532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Peptide Coacervates with Metal\u2013Phenolic Membranes Modulate Glucose Metabolism and Enhance Cancer Immunotherapy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1384-6999","authenticated-orcid":false,"given":"Xin","family":"Zheng","sequence":"first","affiliation":[{"name":"Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Hubei Key Laboratory of Precision Radiation Oncology  Wuhan 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