Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity.

Autor: Yang M; 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., Liu H; Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China., Lou J; Department of Nuclear Medicine, Pudong Medical Center, Fudan University, Shanghai, 201399, China., Zhang J; 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., Zuo C; Department of Nuclear Medicine, the First Affiliated Hospital of Navy Medical University (Changhai Hospital), Shanghai, 200433, China., Zhu M; 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., Zhang X; 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., Yin Y; 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., Zhang Y; 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., Qin S; 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., Zhang H; 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., Fan X; 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., Dang Y; Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China., Cheng C; Department of Nuclear Medicine, the First Affiliated Hospital of Navy Medical University (Changhai Hospital), Shanghai, 200433, China., Cheng Z; Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, 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., Yu F; 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.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Mar; Vol. 20 (9), pp. e2307448. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1002/smll.202307448
Abstrakt: Radium-223 ( 223 Ra) 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 223 Ra remain unclear. Here, it is reported that the 223 Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223 Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223 Ra-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 223 Ra-induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.
(© 2023 The Authors. Small published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: