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.