mIL-21基因转染的Sp2/0瘤苗细胞的抗肿瘤机制探讨

Anti-tumor mechanisms of Sp2/0 tumor vaccine transfected with mIL-21 gene in mice

目的:探讨小鼠IL-21瘤苗-Sp2/0-mIL-21抗肿瘤效应的机制。方法:用流式细胞术检测Sp2/0-mIL-2瘤苗细胞表面MHC-Ⅰ类分子及CD80分子的表达。以瘤苗细胞接种BALB/c小鼠,以CFSE,7-AAD标记,用流式细胞术检测NK细胞、CTL的细胞毒活性。观察肿瘤组织中淋巴细胞的浸润。用RT-PCR检测肿瘤组织中CXC家族趋化因子I-TAC的表达。结果:与对照组相比,瘤苗细胞膜表面MHC-Ⅰ类分子的表达明显上调。瘤苗接种组小鼠NK细胞、CTL的细胞毒活性明显增强。病理分析发现,肿瘤组织中有较多的淋巴细胞浸润并检测到干扰素诱导的T细胞α趋化因子(I-TAC)的表达上调。结论:肿瘤细胞瘤苗Sp2/0-mIL21可增强小鼠的细胞免疫作用,其抗肿瘤机制可能与T细胞的增殖、活化,促进NK细胞的分化成熟,淋巴细胞向肿瘤组织浸润,以及增强NK细胞和CTL的细胞毒活性有关。

AIM： To explore the anti-tumor mechanism of Sp2/0-mlL-21 tumor vaccine in mice. METHODS： The molecules of MHC- Ⅰ and CD80 on the surface of Sp2/0- mIL-21 tumor vaccine were detected by flow cytometry （FCM） respectively. A flow cytometric CFSE-7-AAD cytotoxicity assay was used to detect the cytotoxic activities of NK cells and CTLs. The expression of I-TAC in the tumor tissue was tested by RT-PCR. RESULTS： The expression of MHC- Ⅰmolecule on the surface of tumor vaccine was upregulated obviously. The cytotoxic activities of NK cells and CTLs were significantly enhanced in the mice inoculated with Sp2/0-mIL-21 tumor vaccine compared with the mice inoculated with Sp2/0 tumor cell in control group. The expression of I-TAC in the tumor tissue was up-regulated. The histopathologic section analysis showed more lymphocytes were infiltrated in the tumor tissue. CONCLUSION： Sp2/0- mIL-21 tumor vaccine can induce strong cell-mediated immune response to tumor cells after it was inoculated s. c into mice. The anti-tumor mechanisms induced by Sp2/0 tumor cell vaccine are associated with the proliferation and activation of T lymphocyte, the differentiation and maturity of NK cell, the infiltration of lymphocytes in tumor tissue, and the enharuement of cytotoxic activities of NK cells and CTLs.