Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.
Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.
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DOI：
10.1038/s41467-018-03966-7
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发表时间：
2018-04-27
影响因子：
16.6
通讯作者：
Matsumura N
中科院分区：
文献类型：
--
作者：
Taki M;Abiko K;Baba T;Hamanishi J;Yamaguchi K;Murakami R;Yamanoi K;Horikawa N;Hosoe Y;Nakamura E;Sugiyama A;Mandai M;Konishi I;Matsumura N
蜗牛是诱导上皮-间质转化（EMT）的主要转录因子。在本研究中，我们探讨蜗牛对肿瘤免疫的影响。小鼠卵巢癌细胞的蜗牛敲除抑制免疫能力小鼠的肿瘤生长，与CD8+肿瘤浸润淋巴细胞的增加和髓源性抑制细胞（MDSCs）的减少有关。蜗牛敲低降低了CXCR2配体（CXCL1和CXCL2）的表达，这些趋化因子通过CXCR2将MDSCs吸引到肿瘤中。蜗牛通过NF-kB途径上调CXCR配体，并且很可能通过直接结合启动子。一种CXCR2拮抗剂在表达蜗牛的小鼠肿瘤中抑制MDSC浸润并延缓肿瘤生长。卵巢癌患者血清CXCL1/2升高，与Snail表达、MDSC浸润和总生存期短有关。因此，Snail通过上调CXCR2配体和募集MDSCs诱导癌症进展。阻断CXCR2是一种免疫治疗方法，可抑制EMT中Snail-high肿瘤的进展。蜗牛是一种诱导上皮-间质转化的转录因子。作者发现，在卵巢癌的间充质亚型中，Snail表达通过cxcr2配体介导的髓源性抑制细胞募集，诱导免疫逃避，从而促进肿瘤发生。
Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT. Snail is a transcription factor that induces epithelial-mesenchymal transition. Here the authors show that, in the mesenchymal subtype of ovarian cancer, Snail expression promotes tumorigenesis by inducing immune evasion through CXCR2-ligands-mediated recruitment of myeloid-derived suppressor cells.
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DOI：
10.1186/s13046-015-0247-1
发表时间：
2015-10-26
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
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影响因子：
64.5
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DOI：
10.1152/ajpendo.00347.2013
发表时间：
2014-01-01
影响因子：
5.1
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影响因子：
50.3
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影响因子：
11.5
作者：
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Melero, Ignacio