Authors
Chong Li, Xueyang Liu, Lin Zhu, Ming Liu, Teruaki Konishi, Xiaokun Lou, Li Chen, Jiatao Liao, Yirui Hong, Yun Deng, Mei Xiao, Chunlin Shao, Lin Kong, Xiaomao Guo, Fengtao Su
Published in
Science advances. Volume 12. Issue 35. Pages eaec7590. Aug 28, 2026. Epub Aug 26, 2026.
Abstract
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-κB-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+ 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.
PMID:
42647624
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.
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