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Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells
Li,Ling1; Zou,Jianhua1; Dai,Yunlu2; Fan,Wenpei1,3; Niu,Gang1; Yang,Zhen1; Chen,Xiaoyuan1
2020-11-01
Source PublicationNature Biomedical Engineering
ISSN2157-846X
Volume4Issue:11Pages:1102-1116
Abstract

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.

DOI10.1038/s41551-020-0599-5
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering
WOS SubjectEngineering, Biomedical
WOS IDWOS:000560949200001
Scopus ID2-s2.0-85089534666
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Cited Times [WOS]:27   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorFan,Wenpei; Yang,Zhen; Chen,Xiaoyuan
Affiliation1.Laboratory of Molecular Imaging and Nanomedicine (LOMIN),National Institute of Biomedical Imaging and Bioengineering (NIBIB),National Institutes of Health (NIH),Bethesda,United States
2.Faculty of Health Sciences,University of Macau,Macao
3.State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases,Center of Advanced Pharmaceuticals and Biomaterials,China Pharmaceutical University,Nanjing,China
Recommended Citation
GB/T 7714
Li,Ling,Zou,Jianhua,Dai,Yunlu,et al. Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells[J]. Nature Biomedical Engineering,2020,4(11):1102-1116.
APA Li,Ling,Zou,Jianhua,Dai,Yunlu,Fan,Wenpei,Niu,Gang,Yang,Zhen,&Chen,Xiaoyuan.(2020).Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells.Nature Biomedical Engineering,4(11),1102-1116.
MLA Li,Ling,et al."Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells".Nature Biomedical Engineering 4.11(2020):1102-1116.
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