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

Science advances (2020-04-02)
Chao Wan, Yajie Sun, Yu Tian, Lisen Lu, Xiaomeng Dai, Jingshu Meng, Jing Huang, Qianyuan He, Bian Wu, Zhanjie Zhang, Ke Jiang, Desheng Hu, Gang Wu, Jonathan F Lovell, Honglin Jin, Kunyu Yang
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Glutathione reduced, ≥98.0%
Sigma-Aldrich
Erastin, ≥98% (HPLC)
Sigma-Aldrich
Crystal violet solution
SAFC
2-Mercaptoethanol