Tumor Cell-associated Exosomes Robustly Elicit Anti-tumor Immune Responses through Modulating Dendritic Cell Vaccines in Lung Tumor
DC vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment,however,antitumor effect of DC vaccines based on tumor cell lysates(TCLs)remains unsatisfactory due to poor immunogenicity of tumor antigens.Although tumor-associated exosomes(TAEs)have been reported as a promising antigen for DC vaccines,it remains unclear how TAE-based DC vaccine induced antitumor immunity in lung cancer.Methods:In the present study,we extracted TAEs from the supernatant of tumor cell culture medium,and compared the effect of TAEs with TCLs on DCs.To further evaluate the therapeutic effect of DCTAE,we used immunofluorescence and flow cytometry to evaluate the apoptosis of tumor tissue,tumor-infiltrating CD8+T cells and Tregs in TDLNs and spleen.Then the levels of cytokines of IL-12,IFN-γ,L-10 and TGF-β were quantified by ELISA assays.Results:Our data showed that TAEs were more potent than TCLs to promote DC maturation and enhance MHC cross presentation,which directly contributed to more robust tumor-specific cytotoxic T lymphocyte(CTL)response.More importantly,TAEs reduced the expression of PD-L1 of DCs,thereby led to down-regulated population of Tregs in vitro.Moreover,DCTAE remarkably suppressed the tumor growth and prolonged survival rate in vivo,due to participance of CD8+T cells and decreased Tregs in TDLNs and spleen.Conclusion:TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment.
tumor cell-associated exosome immune response DC vaccine immunosuppression lung tumor
Ce Wang Xue Huang Yingjuan Wu Jingbo Wang Furong Li Guoqing Guo
Department of anatomy,School of Medicine,Jinan University,Guangzhou 510632,China;Shenzhen Key Labora Shenzhen Key Laboratory of Stem cell research and clinical transformation,Guangdong Engineering Tech Department of anatomy,School of Medicine,Jinan University,Guangzhou 510632,China
国际会议
第三届暨南大学粤港澳大湾区医学与健康发展分论坛——医学研究生学术论坛
广州
英文
36-46
2020-11-28（万方平台首次上网日期，不代表论文的发表时间）