Inhibition of Lewis lung carcinoma growth by Toxoplasma gondii through induction of Th1 immune responses and inhibition of angiogenesis.
Inhibition of Lewis lung carcinoma growth by Toxoplasma gondii through induction of Th1 immune responses and inhibition of angiogenesis.
复制标题
DOI：
10.3346/jkms.2007.22.s.s38
复制
发表时间：
2007-09
影响因子：
4.5
通讯作者：
Lee YH
中科院分区：
文献类型：
--
作者：
Kim JO;Jung SS;Kim SY;Kim TY;Shin DW;Lee JH;Lee YH
刚地弓形虫是一种专性细胞内原生动物寄生虫，诱导抗肿瘤活性对某些类型的癌症。然而，关于调节这些效应的免疫机制的信息很少。为此目的，对C57 BL/6小鼠给予T.弓形虫Me 49株或刘易斯肺癌（LLC）细胞。存活率，肿瘤大小，组织病理学，和免疫反应进行了测定，每组和血管生成进行了评估，在体内基质胶塞测定。弓形虫感染（TG注射）小鼠在整个实验期间存活，而携带癌细胞（LLC注射）小鼠在六周内死亡。注射了两种T.与注射LLC的小鼠相比，注射TG/LLC的小鼠的存活率、CD 8 + T细胞百分比、IFN-γ mRNA表达水平、血清IgG 2a滴度和CTL应答显著增加。此外，TG/LLC注射小鼠中的血管生成被显著抑制。TG/LCC注射小鼠中的这些作用相似，或通过添加佐剂Quil-A而增加。然而，与TG注射小鼠相比，TG/LLC注射小鼠显示CD 4+和CD 8 + T细胞百分比、IFN-γ mRNA表达水平以及血清IgG 1和IgG 2a滴度降低。综上所述，我们的结果表明，T。弓形虫感染通过诱导Th 1免疫应答和抗血管生成活性抑制刘易斯肺癌小鼠模型中的肿瘤生长。
Toxoplasma gondii is an obligate intracellular protozoan parasite that induces antitumor activity against certain types of cancers. However, little information is available regarding the immunologic mechanisms that regulate these effects. For this purpose, C57BL/6 mice were administered either the T. gondii Me49 strain orally or Lewis lung carcinoma (LLC) cells intramuscularly. Survival rates, tumor size, histopathology, and immune responses were determined for each group, and angiogenesis was evaluated by in vivo Matrigel plug assay. Toxoplasma-infected (TG-injected) mice survived the entire experimental period, whereas cancer cell-bearing (LLC-injected) mice died within six weeks. Mice injected with both T. gondii and cancer cells (TG/LLC-injected group) showed significantly increased survival rates, CD8+ T-cell percentages, IFN-γ mRNA expression levels, serum IgG2a titers, and CTL responses as compared to the LLC-injected mice. In addition, angiogenesis in the TG/LLC-injected mice was notably inhibited. These effects in TG/LCC-injected mice were similar or were increased by the addition of an adjuvant, Quil-A. However, TG/LLC-injected mice showed decreased percentages of CD4+ and CD8+ T-cells, IFN-γ mRNA expression levels, and serum IgG1 and IgG2a titers as compared to TG-injected mice. Taken together, our results demonstrate that T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and antiangiogenic activity.