IL-10 suppresses IFN-γ-mediated signaling in lung adenocarcinoma
IL-10 suppresses IFN-γ-mediated signaling in lung adenocarcinoma
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IL-10 抑制肺腺癌中 IFN-γ 介导的信号传导
DOI：
10.1007/s10238-020-00626-3
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发表时间：
2020-04-18
影响因子：
4.6
通讯作者：
Fu, Xiangning
中科院分区：
文献类型：
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作者：
Gao, Yi;Lu, Jiawei;Fu, Xiangning
白细胞介素-10（IL-10）是由多种细胞产生的多效性细胞因子。它与癌症进展有关，有时，它似乎有矛盾的影响。IL-10在癌症背景下对免疫组分的影响已被深入研究，但其对癌细胞的影响仍知之甚少。在这项研究中，我们研究了IL-10和IL-10受体1（IL-10 R1）的表达在局部晚期肺腺癌切除术免疫组化。IL-10在上皮内的免疫反应性强于间质。在上皮内或间质区发现的IL-10的量没有预后价值，但IL-10在这两个位置的相对分布与癌症免疫表型有关。肿瘤细胞IL-10 R1的高表达与不良预后显著相关，表明IL-10介导的信号传导可能诱导促进癌症进展的癌细胞内在效应。使用人肺腺癌细胞系的功能分析显示，IL-10不直接影响细胞增殖和迁移。用IL-10孵育癌细胞抑制干扰素-γ（IFN-γ）诱导的STAT 1磷酸化，并抑制IFN-γ靶向基因（如CXCL 9、CXCL 10和PD-L1）的转录。IL-10增强了IFN-γ诱导的SOCS 1和SOCS 3表达，这种作用可能与癌细胞中STAT 1活性下调有关。我们的研究结果为靶向癌细胞上的IL-10作为治疗癌症的潜在策略提供了理论基础。
Interleukin-10 (IL-10) is a pleiotropic cytokine produced by a wide variety of cells. It has been implicated in cancer progression, and at times, it has seemingly contradictory effects. The impact of IL-10 on immune components in the context of cancer has been intensively investigated, but its effect on cancer cells remains poorly understood. In this study, we examined the expression of IL-10 and IL-10 receptor 1 (IL-10R1) in resected locally advanced lung adenocarcinoma by immunohistochemistry. IL-10 immunoreactivity was stronger in intraepithelial regions than in stroma. The amount of IL-10 found either in intraepithelial or in stromal regions had no prognostic value, but the relative distribution of IL-10 in these two locations was related to cancer-immune phenotypes. High expression of IL-10R1 by tumor cells was significantly correlated with poor prognosis, suggesting that IL-10-mediated signaling may induce cancer cell intrinsic effects that promote cancer progression. Functional analysis using human lung adenocarcinoma cell lines revealed that IL-10 did not directly affect cell proliferation and migration. Incubation of cancer cells with IL-10 suppressed interferon-gamma (IFN-gamma)-induced STAT1 phosphorylation and inhibited the transcription of IFN-gamma-targeted genes, such as CXCL9, CXCL10, and PD-L1. IL-10 enhanced IFN-gamma-induced SOCS1 and SOCS3 expression, an effect that might be responsible for the downregulation of STAT1 activity in cancer cells. Our findings provide a rationale for targeting IL-10 on cancer cells as a potential strategy for treating cancer.