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血管内皮钙黏蛋白修饰的树突状细胞疫苗诱导的抗肿瘤免疫

Antitumor immunity induced by VE-cadherin modified DC vaccine.

作者信息

Zhou Jing, Xi Yufeng, Mu Xiyan, Zhao Rongce, Chen Hongdou, Zhang Li, Wu Yang, Li Qiu

机构信息

The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China.

出版信息

Oncotarget. 2017 Jun 27;8(40):67369-67379. doi: 10.18632/oncotarget.18654. eCollection 2017 Sep 15.

DOI:10.18632/oncotarget.18654
PMID:28978039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5620179/
Abstract

Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation. Its damage to the major organs was also evaluated. DC-VEC vaccine resulted in retarded tumor progression and prolonged survival in mice. In DC-VEC group, large amount of immunoglobulin was generated, T cells exhibited greater cytotoxicity against VE-cadherin, and tumor angiogenesis was suppressed. Besides, a decrease of VEGF-A and TGF-β1, and an increase of IL-4 and IFN-γ were observed. CD4 and CD8 T cells were higher, with increased IFN-γ secretion. The percentage of myeloid-derived suppressor cells and regulatory T cells decreased mildly. Also, it had no pathologic changes in major organs. DC-VEC vaccine represents a promising antitumor immunotherapy. The main mechanism is associated with its anti-angiogenesis and immunoregulation response.

摘要

树突状细胞（DCs）是最有效的抗原呈递细胞。人们对用于癌症免疫治疗的DC疫苗产生了浓厚兴趣。此外，血管生成对肿瘤生长至关重要。血管内皮钙黏蛋白在血管生物学功能的各个方面都具有关键作用。在此，我们制备了全血管内皮钙黏蛋白基因修饰的DC疫苗（DC-VEC）。评估了其抗肿瘤免疫及驱动抗肿瘤效应的主要机制。进行了包括抗肿瘤抗体检测、CTL介导的细胞毒性实验、血管密度、免疫调节中细胞及细胞因子变化评估等分析。还评估了其对主要器官的损伤。DC-VEC疫苗导致小鼠肿瘤进展延迟和生存期延长。在DC-VEC组中，产生了大量免疫球蛋白，T细胞对血管内皮钙黏蛋白表现出更大的细胞毒性，并且肿瘤血管生成受到抑制。此外，观察到VEGF-A和TGF-β1减少，IL-4和IFN-γ增加。CD4和CD8 T细胞增多，IFN-γ分泌增加。髓源性抑制细胞和调节性T细胞的百分比轻度下降。而且，其主要器官无病理变化。DC-VEC疫苗是一种有前景的抗肿瘤免疫疗法。主要机制与其抗血管生成和免疫调节反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/619e2890bb0f/oncotarget-08-67369-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/26833698f01b/oncotarget-08-67369-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/aeed245220d3/oncotarget-08-67369-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/fc9f01c1fee5/oncotarget-08-67369-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/c9c91af73766/oncotarget-08-67369-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/9c1ae5937123/oncotarget-08-67369-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/619e2890bb0f/oncotarget-08-67369-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/26833698f01b/oncotarget-08-67369-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/aeed245220d3/oncotarget-08-67369-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/fc9f01c1fee5/oncotarget-08-67369-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/c9c91af73766/oncotarget-08-67369-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/9c1ae5937123/oncotarget-08-67369-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f281/5620179/619e2890bb0f/oncotarget-08-67369-g006.jpg

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