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Ovarian carcinoma cells inhibit T cell proliferation: suppression of IL-2 receptor beta and gamma expression and their JAK-STAT signaling pathway

机译:卵巢癌细胞抑制T细胞增殖:抑制IL-2受体β和γ表达及其JAK-STAT信号通路

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Deficient T cell immune function and intracellular signaling in cancer patients may result from effects of tumors or their products on lymphocytes. Recently, it was demonstrated that several ovarian carcinoma cell lines could produce soluble factors that inhibited T cell proliferation. The aim of this study is to assess the effect of supernatants from 3 ovarian carcinoma cell lines (OVCAR3, CAOV3, SKOV3) on signal transduction elements that are linked to the IL-2R and its JAK-STAT pathway. A profound inhibition of proliferation, lower level of IFN-gamma and higher level of IL-10 gene expression were observed when CD8(+) T cells were co-cultured with supernatants from 3 ovarian carcinoma cell lines. Cell cycle studies on inhibited CD8(+) T cells showed most of them were growth arrested in G(0)/G(1) phase. Western blot analysis showed that tumor supernatants suppressed expression of JAK3 and tyrosine phosphorylation of STAT5. JAK1 was not altered and the inhibition of STAT3 only appeared in OVCAR3 cells. Tumor supernatants also partially blocked induction of IL-2R beta and gamma chains expression. These findings suggest that ovarian carcinoma cells may suppress T cell proliferation through inhibition IL-2 dependent signaling pathways, which may be a mechanism of ovarian carcinoma induced immunosuppression. (C) 2003 Elsevier Inc. All rights reserved. [References: 32]
机译:癌症患者中的T细胞免疫功能不足和细胞内信号传导可能是由于肿瘤或其产物对淋巴细胞的作用所致。最近,证明了几种卵巢癌细胞系可以产生抑制T细胞增殖的可溶性因子。这项研究的目的是评估3种卵巢癌细胞系(OVCAR3,CAOV3,SKOV3)上清液对与IL-2R及其JAK-STAT途径相关的信号转导元件的影响。当CD8(+)T细胞与来自3个卵巢癌细胞系的上清液共培养时,观察到了对增殖的深刻抑制,较低水平的IFN-γ和较高水平的IL-10基因表达。对受抑制的CD8(+)T细胞的细胞周期研究表明,它们中的大多数处于G(0)/ G(1)期停滞状态。 Western印迹分析表明,肿瘤上清液抑制JAK3的表达和STAT5的酪氨酸磷酸化。 JAK1没有改变,STAT3的抑制仅出现在OVCAR3细胞中。肿瘤上清液也部分阻断了IL-2Rβ和γ链表达的诱导。这些发现表明,卵巢癌细胞可以通过抑制IL-2依赖性信号通路抑制T细胞增殖,这可能是卵巢癌诱导的免疫抑制的机制。 (C)2003 Elsevier Inc.保留所有权利。 [参考:32]

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