RT Journal Article SR Electronic T1 Irradiated tumor cell–derived microparticles mediate tumor eradication via cell killing and immune reprogramming JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaay9789 DO 10.1126/sciadv.aay9789 VO 6 IS 13 A1 Wan, Chao A1 Sun, Yajie A1 Tian, Yu A1 Lu, Lisen A1 Dai, Xiaomeng A1 Meng, Jingshu A1 Huang, Jing A1 He, Qianyuan A1 Wu, Bian A1 Zhang, Zhanjie A1 Jiang, Ke A1 Hu, Desheng A1 Wu, Gang A1 Lovell, Jonathan F. A1 Jin, Honglin A1 Yang, Kunyu YR 2020 UL http://advances.sciencemag.org/content/6/13/eaay9789.abstract AB 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.