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

查看全文 作　　者：ring [1]Liang;Xiaolin [1]Liu;Qi [2]Xie;Guoling [3]Chen;Xingyu [1]Li;Yanrui [1]Jia;Beibei [1]Yin;Xun [4]Qu;Yan [1]Li

机构地区：[1]Department of Oncology,Qianfoshan Hospital,Shandong University,Jinan 250014,China;[2]Central Laboratory,Qianfoshan Hospital,Shandong University,Jinan 250014,China;[3]Islet Cell Lab,MedStar Georgetown University Hospital,Washington DC 20007,USA;[4]Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics of Shandong Province,Qilu Hospital,Shandong University,Jinan 250012,China

出　　处：《Chinese Journal of Cancer Research》索引2016年第28卷第4期,共9页

基　　金：supported by Natural Science Foundation of Shandong province,China(No.ZR2010HL015);Natural Science Youth Foundation of Shandong province,China(No.ZR2013HQ017) 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 DCT+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(m DC), 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 interleukin(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 DCT+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 DCT+endostatin group, the proportions of MDSC and TAM(M2 type) were significantly decreased, m DC and TAM(M1 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-17 in tumor tissue, and enhanced the expression of IFN-γ.Conclusions: The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer. 关键词：抗肿瘤作用树突状细胞细胞治疗内皮抑素荷瘤小鼠肿瘤抗原肺癌脉冲

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

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