Irradiated tumor cell-derived microparticles mediate tumor eradication via cell killing and immune reprogramming

• Published in: Science advances Vol. 6; no. 13; p. eaay9789
• Main Authors: Wan, Chao, Sun, Yajie, Tian, Yu, Lu, Lisen, Dai, Xiaomeng, Meng, Jingshu, Huang, Jing, He, Qianyuan, Wu, Bian, Zhang, Zhanjie, Jiang, Ke, Hu, Desheng, Wu, Gang, Lovell, Jonathan F, Jin, Honglin, Yang, Kunyu
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.03.2020
• Subjects: Cancer; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aay9789

Radiotherapy (RT) is routinely used in cancer treatment, but expansion of its clinical indications remains challenging. The mechanism underlying the radiation-induced bystander effect (RIBE) is not understood and not therapeutically exploited. We suggest that the RIBE is predominantly mediated by irradiated tumor cell-released microparticles (RT-MPs), which induce broad antitumor effects and cause immunogenic death mainly through ferroptosis. Using a mouse model of malignant pleural effusion (MPE), we demonstrated that RT-MPs polarized microenvironmental M2 tumor-associated macrophages (M2-TAMs) to M1-TAMs and modulated antitumor interactions between TAMs and tumor cells. Following internalization of RT-MPs, TAMs displayed increased programmed cell death ligand 1 (PD-L1) expression, enhancing follow-up combined anti-PD-1 therapy that confers an ablative effect against MPE and cisplatin-resistant MPE mouse models. Immunological memory effects were induced.