Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment
Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment
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IL-23通过肿瘤微环境中M2巨噬细胞和中性粒细胞浸润介导的乳腺癌促癌作用
DOI：
10.1016/j.bbrc.2016.12.048
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发表时间：
2017-01-22
影响因子：
3.1
通讯作者：
Gao, Xiang
中科院分区：
文献类型：
--
作者：
Nie, Wen;Yu, Ting;Gao, Xiang
白细胞介素23（IL-23）是一种炎症细胞因子，在自身免疫性疾病以及肿瘤发生中起重要作用。然而，IL-23在肿瘤进展中的作用仍存在争议，其潜在机制仍不清楚。在此，我们建立了一个稳定的过表达IL-23的细胞系，以证明IL-23通过诱导肿瘤相关炎症和缺乏免疫监视来促进肿瘤生长和肺转移。IL-23促进肿瘤相关的炎症反应，例如M2巨噬细胞、中性粒细胞的浸润以及它们向肿瘤组织中分泌的免疫抑制性细胞因子转化生长因子-β（TGF-β）、IL-10和血管内皮生长因子（VEGF）的升高，同时基质金属蛋白酶MMP 9的增加。此外，IL-23增加肿瘤中内皮标志物CD 31和增殖标志物Ki 67的表达。此外，IL 23通过减少CD 4（+）和CD 8（+）T细胞向肿瘤组织中的浸润而诱导免疫抑制。总之，IL-23在肿瘤进展中是一个重要的分子，它同时促进促肿瘤炎症过程，如血管生成、免疫抑制性细胞因子以及M2巨噬细胞和中性粒细胞的浸润，并通过减少CD 4（+）T细胞和CD 8（+）T细胞来抑制抗肿瘤免疫应答。(C)2016 Elsevier Inc. All rights reserved.
Interleukin 23 (IL-23) is an inflammatory cytokine which plays a vital role in autoimmune diseases as well as in tumorigenesis. However, the role of IL-23 in tumor procession is still controversial and the underlying mechanism remains unclear. Here we established a stable cell line overexpressing IL-23 to prove that IL-23 promoted tumor growth and pulmonary metastasis through induction of tumor-related inflammation and absence of immune surveillance. IL-23 promotes tumor-associate inflammatory response such as infiltration of M2 macrophages, neutrophils and their elevated secretions of immunosuppressive cytolcines transforming growth factor-beta (TGF-beta), IL-10 and vascular endothelial growth factor (VEGF) into tumor tissues, meanwhile the increase of the matrix metalloprotease MMP9. In addition, IL-23 increases the expression of the endothelial marker CD31 and proliferative marker Ki67 in tumors. Moreover, IL23 induces immunosuppression though reducing the infiltration of CD4(+) and CD8(+)T cells into tumor tissues. In conclusion, IL-23 is a considerable molecular in tumor progression, which simultaneously facilitates processes of pro-tumor inflammation, such as angiogenesis, immunosuppressive cytolcines as well as infiltrations of M2 macrophages and neutrophils, and suppresses antitumor immune responses through reduction of CD4(+) T cells and CD8(+) T cells. (C) 2016 Elsevier Inc. All rights reserved.