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Adv."],"published-print":{"date-parts":[[2026,8,28]]},"abstract":"<jats:p>\n                    Radiotherapy augments immunotherapy, yet conventional 2 Gy x-ray fractions largely induce apoptosis, whereas robust immunogenic cell death (ICD) is more commonly associated with higher-dose irradiation regimens. Here, we reveal a dose-independent, high-LET-specific paradigm: a physical dose of 2 Gy of carbon ions provokes antitumor immunity. Carbon ions redirect death wiring to MLKL-dependent necroptosis and trigger an NF-\u03baB-driven inflammatory cascade (IL1A\/B, CXCL1\/2\/3), surpassing 8 Gy x-rays in immunogenicity despite lower direct tumor cell-killing capacity. Multi-omics analyses identify clustered DNA damage-driven super-enhancer remodeling as an epigenetic switch that suppresses cIAP1\/2-caspase-8-mediated apoptosis while licensing inflammatory necroptosis. Pharmacologic inhibition of MLKL abolishes these responses to carbon ion radiotherapy (CIRT). In vivo, 2 Gy CIRT drives abscopal response with increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and function. Together, these findings establish CIRT as a feasible, immune-stimulatory radiotherapy converting local exposure into systemic control via super-enhancer-mediated reprogramming of death and inflammation, providing a mechanistic rationale to integrate carbon ions into next-generation radio-immunotherapy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec7590","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:59:39Z","timestamp":1787767179000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Carbon ion irradiation at a clinically used dose rewires super-enhancers to drive necroptosis and systemic immunity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7988-3069","authenticated-orcid":true,"given":"Chong","family":"Li","sequence":"first","affiliation":[{"name":"Cancer Institute, Department of Radiation Oncology, Fudan University 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