Sun H, Kundu N, Dorsey R, Jackson M J, Fulton A M
Greenebaum Cancer Center and Deparment of Pathology, University of Maryland, Baltimore, USA.
J Immunother. 2001 Mar-Apr;24(2):138-43.
Several laboratories have reported marked tumor inhibition when the cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of tumor cells. To identify critical effector molecules, we compared the expression of the chemokine crg-2, the murine homolog of human inducible protein 10 (human IP-10) in murine mammary tumors derived from the transplantation of six IL-10 expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma]) was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells in vitro show that mammary epithelial tumor cells, in the absence of host elements, can express IP-10 and Mig in response to induction with either lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN-gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction differ somewhat for the two chemokines, with IP-10 showing slower induction and less rapid decline. Because both Mig and IP-10 are chemotactic for tumor-infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes in these tumors. Consistent with the upregulation of Mig and IP-10, we saw significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells in tumors with elevated levels of both chemokines.
几个实验室报告称，当细胞因子白细胞介素-10（IL-10）作为转基因在多种肿瘤细胞中过表达时，会出现显著的肿瘤抑制。为了确定关键效应分子，我们比较了趋化因子crg-2（人诱导蛋白10（人IP-10）的小鼠同源物）在源自肿瘤细胞系66.1的六个表达IL-10的克隆、亲本66.1或66-新细胞移植产生的小鼠乳腺肿瘤中的表达。我们观察到，与66-新细胞相比，在所有检测的表达IL-10的肿瘤中，IP-10 mRNA水平升高。在亲本66.1肿瘤中未检测到IP-10 mRNA。密切相关的趋化因子Mig（干扰素-γ[IFN-γ]诱导的单核因子）在所有表达IL-10的肿瘤中也被诱导。体外培养肿瘤细胞的研究表明，在没有宿主成分的情况下，乳腺上皮肿瘤细胞可单独响应脂多糖（LPS）或IFN-γ的诱导而表达IP-10和Mig。LPS加IFN-γ的组合导致IP-10 RNA的诱导作用更强。两种趋化因子的诱导动力学有所不同，IP-10的诱导较慢且下降不那么迅速。由于Mig和IP-10对肿瘤浸润淋巴细胞都有趋化作用，我们检查了这些肿瘤中CD4+和CD8+淋巴细胞的存在情况。与Mig和IP-10的上调一致，我们发现在两种趋化因子水平升高的肿瘤中，CD8+细胞数量显著增加而CD4+细胞增加较少。
