Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma

作     者：ring Liang Xiaolin Liu Qi Xie Guoling Chen Xingyu Li Yanrui Jia Beibei Yin Xun Qu Yan Li 

作者机构：Department of OncologyQianfoshan HospitalShandong UniversityJinan 250014China Central LaboratoryQianfoshan HospitalShandong UniversityJinan 250014China Islet Cell LabMedStar Georgetown University HospitalWashington DC 20007USA Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics of Shandong ProvinceQilu HospitalShandong UniversityJinan 250012China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2016年第28卷第4期

页      面：452-460页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 071005[理学-微生物学] 090102[农学-作物遗传育种] 10[医学] 

基　　金：supported by Natural Science Foundation of Shandong province,China(No.ZR2010HL015) Natural Science Youth Foundation of Shandong province,China(No.ZR2013HQ017) 

主　　题：Endostatin DC-T cells lung cancer cellular therapy tumor microenvironment 

摘      要：Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC- T＋endostatin group, DC-T group, and phosphate-buffered saline （PBS） control group. Microvessel density （MVD） of tumor tissue in tumor-bearing mice was determined by immunohistochemistry （IHC）. The expressions of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） were determined by Western blotting and IHC staining. The proportions of CD8＋ T cells, mature dendritic cells （mDC）, tumor-associated macrophages [TAM （M1/M2）], and myeloid-derived suppressor cells （MDSC） in suspended cells of tumor tissue were determined by flow cytometry. The expressions of inter｜eukin （IL）-6, IL-10, IL-17, transforming growth factor-β（TGF-β） and interferon-γ （IFN-γ） in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay （ELISA）. Results： DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC- T＋endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ, and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC- T＋endostatin group, the proportions of MDSC and TAM （M2 type） were significantly decreased, mDC and TAM （Nil type） were up-regulated, and CD8＋ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and IL-1