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Herein, a T cell membrane (TCM)\u2010coated biomimetic magnesium carbonate (MgCO\n                    <jats:sub>3<\/jats:sub>\n                    )\/Fe\u2010CD hybrid nanozyme system loaded with the Pyruvate kinase M2 (PKM2) activator TEPP\u201046 (TFMP) is developed, designed to simultaneously induce mitochondrial metabolic reprogramming in both T cells and tumor cells following radiotherapy (RT). The TCM coating enables TFMP to specifically target tumor tissues that highly express PD\u2010L1, where it competitively binds to PD\u2010L1 and thereby alleviates immune checkpoint\u2010mediated T cell suppression. Upon X\u2010ray irradiation, TFMP continuously catalyzes the conversion of radiotherapy\u2010generated hydrogen peroxide into hydroxyl radicals, thereby sustaining reactive oxygen species production, which leads to mitochondrial damage and immunogenic cell death in tumor cells. Moreover, TFMP can neutralize the acidic tumor microenvironment, while the released Mg\n                    <jats:sup>2+<\/jats:sup>\n                    and TEPP\u201046 further augment T cell activation and mitochondrial function, thereby increasing the production of ATP and granzyme B, which effectively eliminate residual tumor cells. Experimental results demonstrate that the combination of TFMP and RT can significantly inhibit tumor progression and activate anti\u2010tumor immunotherapy. This TFMP enhances the efficacy of breast cancer radioimmunotherapy, offering a foundation for developing more comprehensive therapeutic approaches of breast cancer to achieve clinical benefits.\n                  <\/jats:p>","DOI":"10.1002\/advs.202515097","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:32:02Z","timestamp":1762162322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differentiated T Lymphocytes and Cancer Cell Mitochondrial Metabolism to Enhance Radioimmunotherapy by a Biomimetic Nanozyme System"],"prefix":"10.1002","volume":"13","author":[{"given":"Hanyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oncology Surgery Harbin Medical University Cancer Hospital  Harbin 150000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery Harbin Medical University Cancer Hospital  Harbin 150000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantong","family":"Lu","sequence":"additional","affiliation":[{"name":"Digestive Diseases Center The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen 518107 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery Harbin Medical University Cancer Hospital  Harbin 150000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery Harbin Medical University Cancer Hospital  Harbin 150000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery The Second Affiliated Hospital of Guangxi Medical University  Nanning 530000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-6598","authenticated-orcid":false,"given":"Shipeng","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery The Second Affiliated Hospital of Guangxi Medical University  Nanning 530000 China"},{"name":"Research Center of Nanomedicine Technology The Second Affiliated Hospital of Guangxi Medical University  Nanning 530000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery Harbin Medical University Cancer Hospital  Harbin 150000 China"},{"name":"NHC Key Laboratory of Cell Transplantation Harbin Medical University  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v022a20"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v052a04"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000074"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000046"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000056"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000067"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2025.06.036"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00271E"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01803-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.734256"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0441-y"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00541-y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.81609"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.035"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-01000-4"},{"key":"e_1_2_7_16_1","first-page":"140","volume":"34","author":"Gong L.","year":"2018","journal-title":"Acta. 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