Department of anatomy, School of Medicine, Jinan University, Guangzhou 510632, China.
Shenzhen Key Laboratory of Stem cell research and clinical transformation, Guangdong Engineering Technology Research Center of Stem cell and Cell therapy, Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.
Int J Biol Sci. 2020 Jan 14;16(4):633-643. doi: 10.7150/ijbs.38414. eCollection 2020.
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. : 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 DC, 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. : 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 . Moreover, DC remarkably suppressed the tumor growth and prolonged survival rate , due to participance of CD8 T cells and decreased Tregs in TDLNs and spleen. : TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment.
基于树突状细胞（DC）疫苗的免疫疗法作为一种治疗癌症的新型治疗策略正在兴起，然而，由于肿瘤抗原的免疫原性差，基于肿瘤细胞裂解物（TCL）的 DC 疫苗的抗肿瘤效果仍不尽人意。虽然肿瘤相关外泌体（TAE）已被报道为 DC 疫苗的一种有前途的抗原，但 TAE 基 DC 疫苗如何诱导肺癌中的抗肿瘤免疫仍不清楚。在本研究中，我们从肿瘤细胞培养液上清中提取 TAE，并比较了 TAE 与 TCL 对 DC 的作用。为了进一步评估 DC 的治疗效果，我们使用免疫荧光和流式细胞术评估肿瘤组织、肿瘤浸润性 CD8 T 细胞和 Tregs 在 TDLNs 和脾脏中的凋亡。然后通过 ELISA 测定法定量测定细胞因子 IL-12、IFN-γ、L-10 和 TGF-β 的水平。我们的数据表明，TAE 比 TCL 更能促进 DC 成熟和增强 MHC 交叉呈递，这直接导致更强的肿瘤特异性细胞毒性 T 淋巴细胞（CTL）反应。更重要的是，TAE 降低了 DC 中 PD-L1 的表达，从而导致 Tregs 群体减少。此外，由于 TDLNs 和脾脏中 CD8 T 细胞和 Tregs 的减少，DC 显著抑制了肿瘤生长并延长了存活率。TAE 可以通过触发更强的 DC 介导的免疫反应和减少肿瘤微环境中的 Tregs 来改善疫苗引发的免疫治疗。
