Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Laboratory of Thoracic Surgery, Tongji Hospital, Tongji Medical College, University of Science and Technology, 1095 Jie Fang Avenue, Wuhan, 430030, Hubei, China.
Clin Exp Med. 2020 Aug;20(3):449-459. doi: 10.1007/s10238-020-00626-3. Epub 2020 Apr 18.
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-γ (IFN-γ)-induced STAT1 phosphorylation and inhibited the transcription of IFN-γ-targeted genes, such as CXCL9, CXCL10, and PD-L1. IL-10 enhanced IFN-γ-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.
白细胞介素-10（IL-10）是一种由多种细胞产生的多功能细胞因子。它已被牵涉到癌症的进展中，并且有时具有看似矛盾的作用。IL-10 对癌症环境中免疫成分的影响已经得到了深入研究，但它对癌细胞的影响仍知之甚少。在这项研究中，我们通过免疫组织化学检查了切除的局部晚期肺腺癌中 IL-10 和 IL-10 受体 1（IL-10R1）的表达。上皮内区域的 IL-10 免疫反应性强于基质。上皮内或基质中发现的 IL-10 数量没有预后价值，但这两个位置的 IL-10 相对分布与癌症免疫表型有关。肿瘤细胞中 IL-10R1 的高表达与预后不良显著相关，这表明 IL-10 介导的信号可能诱导癌症细胞内在效应，从而促进癌症进展。使用人肺腺癌细胞系进行的功能分析表明，IL-10 不会直接影响细胞增殖和迁移。将癌细胞与 IL-10 孵育可抑制干扰素-γ（IFN-γ）诱导的 STAT1 磷酸化，并抑制 IFN-γ 靶向基因（如 CXCL9、CXCL10 和 PD-L1）的转录。IL-10 增强了 IFN-γ 诱导的 SOCS1 和 SOCS3 表达，这种作用可能是癌细胞中 STAT1 活性下调的原因。我们的研究结果为针对癌细胞上的 IL-10 作为治疗癌症的潜在策略提供了依据。
