Song Zhenchuan, Guo Chenjun, Li Yong, Tan Bibo, Fan Liqiao, Xiao Jianwei
Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Exp Ther Med. 2012 Feb;3(2):319-323. doi: 10.3892/etm.2011.394. Epub 2011 Nov 28.
T cell-mediated antitumor immunity is a cellular immune response that requires two signals. The dendritic cell (DC) has been considered as the most efficient antigen-presenting cell (APC). It plays essential roles in the induction, regulation and maintenance of antitumor immunity in humans. The 4-1BB/4-1BB ligand (4-1BBL) pathway plays crucial roles in immune response, tumor immunity and autoimmune diseases through transduction of T cell co-stimulatory signals. The aim of this study was to generate the preparation protocol for a DC vaccine transfected with gastric cancer cell total ribonucleic acid (RNA) carrying the 4-1 BBL gene in vitro and to investigate its antitumor effects in murine forestomach carcinoma (MFC). The vaccine was prepared by transfecting MFC total RNAs carrying the 4-1BBL gene into the DCs that were isolated from 615 mouse bones. The T cell proliferation rate in the MFC/4-1BBL/DC group was higher than that in the DC group. The tumor cell kill rate in the MFC/4-1BBL/DC group was higher than that in the DC group. ELISA analysis showed that IL-12 and IFN-γ in the MFC/4-1BBL/DC group were more highly expressed compared to the other group. Collectively, our data demonstrate that the DC vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene has a stronger ability to kill gastric cancer cells through promoting T cell proliferation and enhancing the ability of cytotoxic T lymphocytes (CTLs) to kill gastric carcinoma cells and to secrete IL-12 and IFN-γ. Our results provide an effective therapeutic strategy for treating gastric cancer using a DC vaccine.
T细胞介导的抗肿瘤免疫是一种需要两个信号的细胞免疫反应。树突状细胞（DC）被认为是最有效的抗原呈递细胞（APC）。它在人类抗肿瘤免疫的诱导、调节和维持中发挥着重要作用。4-1BB/4-1BB配体（4-1BBL）途径通过转导T细胞共刺激信号，在免疫反应、肿瘤免疫和自身免疫性疾病中发挥关键作用。本研究的目的是制定体外转染携带4-1BBL基因的胃癌细胞总核糖核酸（RNA）的DC疫苗制备方案，并研究其对小鼠前胃癌（MFC）的抗肿瘤作用。通过将携带4-1BBL基因的MFC总RNA转染到从615小鼠骨骼中分离的DC中来制备疫苗。MFC/4-1BBL/DC组的T细胞增殖率高于DC组。MFC/4-1BBL/DC组的肿瘤细胞杀伤率高于DC组。ELISA分析表明，与其他组相比，MFC/4-1BBL/DC组中IL-12和IFN-γ的表达更高。总体而言，我们的数据表明，转染携带4-1BBL基因的胃癌细胞总RNA的DC疫苗具有更强的杀伤胃癌细胞的能力，其通过促进T细胞增殖以及增强细胞毒性T淋巴细胞（CTL）杀伤胃癌细胞和分泌IL-12及IFN-γ的能力来实现。我们的结果为使用DC疫苗治疗胃癌提供了一种有效的治疗策略。
