Alpha‐Emitter Radium‐223 Induces STING‐Dependent Pyroptosis to Trigger Robust Antitumor Immunity
Source abstract
Abstract
Abstract Radium‐223 (223Ra) is the first‐in‐class alpha‐emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double‐strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223Ra remain unclear. Here, it is reported that the 223Ra irradiation induces the pro‐inflammatory damage‐associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223Ra‐induced DNA damage leads to the activation of stimulator of interferon genes (STING)‐mediated DNA sensing pathway, which is critical for NLRP3 inflammasome‐dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha‐emitter 223Ra‐induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: interferon and immune responses · Inflammasome and immune disorders · Ubiquitin and proteasome pathways
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Nuclear Medicine Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200072 China
Institute of Nuclear Medicine Tongji University School of Medicine Shanghai 200072 China
Clinical Translation Research Center Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai 200433 China
Department of Nuclear Medicine Pudong Medical Center Fudan University Shanghai 201399 China
Department of Nuclear Medicine the First Affiliated Hospital of Navy Medical University (Changhai Hospital) Shanghai 200433 China
State Key Laboratory of Drug Research Molecular Imaging Center Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China
Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery Yantai Shandong 264117 China
Funding
National Natural Science Foundation of China · Government of Pudong New Area · Changhai Hospital of Shanghai · Shanghai Shenkang Hospital Development Center
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