Irradiated tumor cell–derived microparticles mediate tumor eradication via cell killing and immune reprogramming
Menée à l'aide de lignées cellulaires et d'un modèle murin, cette étude met en évidence un mécanisme par lequel les microparticules issues des cellules cancéreuses irradiées favorisent l'éradication de la tumeur en modifiant la polarité des macrophages du microenvironnement tumoral ainsi que les interactions de ces derniers avec les cellules cancéreuses
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.
Science Advances 2020