细胞毒性T细胞
膜联蛋白A5
免疫系统
磷脂酰丝氨酸
细胞凋亡
癌症研究
吞噬作用
坏死
膜联蛋白
免疫原性细胞死亡
免疫学
免疫疗法
生物
流式细胞术
生物化学
体外
磷脂
遗传学
膜
作者
Ling Li,Jianhua Zou,Yunlu Dai,Wenpei Fan,Gang Niu,Zhèn Yáng,Xiaoyuan Chen
标识
DOI:10.1038/s41551-020-0599-5
摘要
Cancer immunotherapies, particularly therapeutic vaccination, do not typically generate robust anti-tumour immune responses. Here, we show that the intratumoral burst release of the protein annexin A5 from intravenously injected hollow mesoporous nanoparticles made of diselenide-bridged organosilica generates robust anti-tumour immunity by exploiting the capacity of primary tumours to act as antigen depots. Annexin A5 blocks immunosuppressive apoptosis and promotes immunostimulatory secondary necrosis by binding to the phagocytic marker phosphatidylserine on dying tumour cells. In mice bearing large established tumours, the burst release of annexin A5 owing to diselenide-bond cleavage under the oxidizing conditions of the tumour microenvironment and the reducing intracellular conditions of tumour cells induced systemic cytotoxic T-cell responses and immunological memory associated with tumour regression and the prevention of relapse, and led to complete tumour eradication in about 50% of mice with orthotopic breast tumours. Reducing apoptosis signalling via in situ vaccination could be a versatile strategy for the generation of adaptive anti-tumour immune responses.
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