文献类型：期刊文献

英文题名：Carbon ion radiotherapy triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy in mice

作者：Zhou, Heng[1,2,3];Tu, Chen[4];Yang, Pengfei[1,2,3];Li, Jin[1,2,5];Kepp, Oliver[6];Li, Haining[7];Zhang, Liying[8];Zhang, Lixin[8];Zhao, Yang[4];Zhang, Tianyi[1,2,3];Sheng, Chengyan[5];Wang, Jufang[1,2,3]

第一作者：Zhou, Heng

通信作者：Zhou, H[1];Zhou, H[2];Wang, JF[3]

机构：[1]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Nanchang Rd 509, Lanzhou 730000, Gansu, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Nanchang Rd 509, Lanzhou 730000, Gansu, Peoples R China;[3]Univ Chinese Acad Sci, Sch Nucl Sci & Technol, Beijing, Peoples R China;[4]Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Dermatol, Xian, Shaanxi, Peoples R China;[5]Lanzhou Univ, Sch Nucl Sci & Technol, Lanzhou, Gansu, Peoples R China;[6]Sorbonne Univ, Univ Paris, INSERM, Equipe Labellisee Ligue Canc,Ctr Rech Cordeliers, Paris, France;[7]Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Sci, Lanzhou, Gansu, Peoples R China;[8]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China

第一机构：Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Nanchang Rd 509, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Nanchang Rd 509, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Nanchang Rd 509, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Univ Chinese Acad Sci, Sch Nucl Sci & Technol, Beijing, Peoples R China.

年份：2022

卷号：11

期号：1

外文期刊名：ONCOIMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-85127251325);WOS:【SCI-EXPANDED(收录号:WOS:000782141400001)】；

基金：We would like to thank Qingfeng Wu and Dan Xu from the Institute of Modern Physics, CAS, for their assistance with flow cytometry and radiotherapy. This work was supported by the Hundred-Talent Program of the Chinese Academy of Sciences (NO. 29Y763050, Heng Zhou), the National Nature Science Foundation of China (NO. 11905264, Heng Zhou and NO. 82003356, Chen Tu and NO. 82004094, Liying Zhang), the Science and Technology Research Project of Gansu Province (NO. 17JR5RA307 and NO. 145RTSA012, Jufang Wang).

语种：英文

外文关键词：Carbon ion radiotherapy; immunogenic cell death; melanoma; anti-PD-1 therapy

摘要：Carbon ion radiotherapy (CIRT) is an emerging type of radiotherapy for the treatment of solid tumors. In recent years, evidence accumulated that CIRT improves the therapeutic outcome in patients with otherwise poor response to immune checkpoint blockade. Here, we aimed at identifying the underlying mechanisms of CIRT-induced tumor immunogenicity and treatment efficacy. We used human U2OS osteosarcoma cells for the in vitro assessment of immunogenic cell death and established several in vivo models of melanoma in mice. We treated the animals with conventional radiation, CIRT, PD-1-targeting immune checkpoint blockade or a sequential combinations of radiotherapy with checkpoint blockade. We utilized flow cytometry, polyacrylamide gel electrophoresis (PAGE) and immunoblot analysis, immunofluorescence, immunohistochemistry, as well as enzyme-linked immunosorbent assays (ELISA) to assess biomarkers of immunogenic cell death in vitro. Treatment efficacy was studied by tumor growth assessment and the tumor immune infiltrate was analyzed by flow cytometry and immunohistochemistry. Compared with conventional radioimmunotherapy, the combination of CIRT with anti-PD-1 more efficiently triggered traits of immunogenic cell death including the exposure of calreticulin, the release of adenosine triphosphate (ATP), the exodus of high-mobility group box 1 (HMGB1) as well as the induction of type-1 interferon responses. In addition, CIRT plus anti-PD-1 led to an increased infiltration of CD4(+), and CD8(+) lymphocytes into the tumor bed, significantly decreased tumor growth and prolonged survival of melanoma bearing mice. We herein provide evidence that CIRT-triggered immunogenic cell death, enhanced tumor immunogenicity and improved the efficacy of subsequent anti-PD-1 immunotherapy.