{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:06:28Z","timestamp":1777633588105,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Excess extracellular acidity is a defining barrier to effective antitumor immunity in solid tumors. Systemic buffers only partially correct tumor acidity and seldom rescue suppressed effector immunity. Here, we developed a spatially programmed electrochemical therapy (ECT\n                    <jats:sub>Fe<\/jats:sub>\n                    ) integrating a central sacrificial iron anode with peripheral platinum cathodes to engineer the tumor microenvironment\n                    <jats:italic>in situ<\/jats:italic>\n                    . This configuration enables concurrent acidotoxic and ferroptosis-associated tumor debulking in the core, while controlled peritumoral pH relief restores immune cell function. We combined ECT\n                    <jats:sub>Fe<\/jats:sub>\n                    with intramuscular delivery of a plasmid encoding anti-PD-1 single-chain antibody (pICI) for sustained checkpoint blockade. In aggressive 4T1-luc triple-negative breast cancer (TNBC), ECT\n                    <jats:sub>Fe<\/jats:sub>\n                    markedly enhanced PD-1 blockade efficacy, inducing tumor regression and prolonged survival versus monotherapies. In B16 melanoma, ECT\n                    <jats:sub>Fe<\/jats:sub>\n                    alone achieved robust tumor control with limited additional benefit from PD-1 blockade, revealing tumor-context-dependent interaction. Mechanistically, Fe-anode reactions generated an acidic, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    -rich core with elevated oxidative stress and GPX4 suppression\u2014consistent with ferroptosis\u2014while Pt-cathode-mediated alkalinization (pH 6.6\u20137.0) preserved CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell activity, promoted M1-like macrophage polarization, and reduced regulatory T cells. Collectively, spatially programmed electrochemistry reconditions the tumor microenvironment to sensitize immunologically \u201ccold\u201d TNBC to PD-1 blockade, offering a controllable and translatable strategy to improve checkpoint immunotherapy.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1819923","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:46:12Z","timestamp":1777437972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatially programmed Fe and Pt electrode-driven electrochemistry reconditions the tumor microenvironment and sensitizes triple-negative breast cancer to PD-1 Blockade"],"prefix":"10.3389","volume":"16","author":[{"given":"Jia","family":"Qin","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyao","family":"Yang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijie","family":"Xie","sequence":"additional","affiliation":[{"name":"Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanling","family":"Lu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology\/Gastric Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, 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