Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy  

作　　者：Yuhan Zhou Ting Ye Chengzhi Ye Chao Wan Siyue Yuan Yushuai Liu Tianyu Li Fagang Jiang Jonathan F.Lovell Honglin Jin Jing Chen 

机构地区：[1]Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,PR China [2]Department of Pediatrics,Renmin Hospital of Wuhan University,Wuhan,430060,PR China [3]Department of Ophthalmology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,PR China [4]Department of Biomedical Engineering,University at Buffalo,State University of New York.Buffalo,New York,14260,USA [5]College of Biomedicine and Health and College of Life Science and Technology,Huazhong Agricultural University,Wuhan,430070,China

出　　处：《Bioactive Materials》2022年第3期541-553,共13页生物活性材料（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81773285,81874233 and 82022040);Health Commission of Hubei Province scientific research project(WJ2021Z004);Scientific Research Project of Hubei Provincial Health and Family Planning Commission,China(WJ2015MB017 to J.C.).

摘　　要：Autologous tumor cells and cell-derived secretions(CDS)can induce antitumor immune responses.The conditions in which cells are cultured and treated impact CDS,and cellular insults alter their composition and function.In this study,we generated CDS from tumor cells exposed to normal culture conditions,hypoxia,cisplatin,radiotherapy,photodynamic therapy,or hypochlorous acid(HOCl).In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia,cisplatin,radiotherapy or photodynamic therapy.To improve HOCl-CDS activity at the tumor site,we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold.When injected intratumorally,the HOCl-CDS hydrogel promoted tumor cell death,cytotoxic T lymphocyte infiltration,and tumor-associated macrophage reprogramming towards an M1 phenotype.The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma.Furthermore,hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade.These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

关 键 词：Cancer immunotherapy HYDROGEL MELITTIN Anti-PD-1 Cell-derived secretions 

分 类 号：R730.51[医药卫生—肿瘤]