{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:14:44Z","timestamp":1788437684868,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Iron overload is a common metabolic disturbance in cancer and contributes to poor outcomes in renal cell carcinoma (RCC), yet its effects on the tumour immune microenvironment remain unclear. Here we identify a previously unrecognized immunosuppressive axis in which iron overload downregulates the palmitoyltransferase ZDHHC12 in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, leading to impaired palmitoylation of the mitochondrial protein FDX1. This stabilizes FDX1 and drives cuproptosis, a recently described copper\u2010dependent cell death pathway, thereby compromising T cell effector function and diminishing responses to immune checkpoint blockade. To restore T cell activity, we engineered lipid nanoparticles (ZDHHC12\u2010LNPs) for the delivery of Zdhhc12. These nanoparticles exhibited optimal physicochemical properties, efficiently restored FDX1 palmitoylation, rescued CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell function, and synergized with PD\u20101 blockade in preclinical RCC models without inducing systemic toxicity. Our findings uncover the iron\u2010ZDHHC12\u2010FDX1 axis as a metabolic checkpoint of T cell immunity and demonstrate a nanotechnology\u2010based strategy to overcome iron\u2010driven immunosuppression, offering translational potential for patients with iron\u2010overloaded RCC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202600078","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:30:15Z","timestamp":1781001015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Materials\u2010Guided Gene\u2010Ionizable Lipid Nanoparticles to Reverse Iron\u2010Associated Immune Resistance in Renal Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Xin","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Urology The Second Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Uro\u2010Oncology Institute of Central South University  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