CLIN CANCER RES：免疫微环境通过巨噬细胞分泌的IL-6诱导结直肠癌耐药

2017-12-10 MedSci MedSci原创

肿瘤相关巨噬细胞（TAM）与肿瘤患者不良预后有关。但TAM在结直肠癌中的作用一直存在争议。CLIN CANCER RES近期发表了一篇文章，研究结直肠癌中TAM的功能、机制和临床意义。

肿瘤相关巨噬细胞（TAM）与肿瘤患者不良预后有关。但TAM在结直肠癌中的作用一直存在争议。CLIN CANCER RES近期发表了一篇文章，研究结直肠癌中TAM的功能、机制和临床意义。

作者使用免疫组化方法检测结直肠癌组织中巨噬细胞浸润（CD68），P-gp和Bcl2表达情况。在体内及体外实验中将TAM和结直肠癌细胞共培养评估TAM对结直肠癌耐药的影响。利用细胞因子抗体芯片、ELISA、中和性抗体和荧光报告分析等研究机制。研究结果表明，TAM浸润与结直肠患者耐药有关。结直肠癌微环境中的巨噬细胞增加结直肠癌耐药能力并通过分泌IL-6降低药物诱导的细胞凋亡，这一效果可以被中和性IL-6抗体阻断。巨噬细胞分泌的IL-6活化结直肠癌中的IL6R/STAT3通路，活化的STAT3转录抑制肿瘤异质性miR-204-5p。后续实验证明miR-204-5p是调节TAM诱导的结直肠癌耐药的功能性靶标。miR-155-5p，一种调节C/EBPβ关键的miRNA，在TAM中通常下调，导致C/EBPβ表达增加。C/EBPβ可以活化TAM的IL-6，TAM分泌的IL-6通过激活结直肠癌细胞中IL-6R/STAT3/miR-204-5p通路诱导耐药。

文章最后认为，这些数据表明TAM中miR-155-5p/C/EBPβ/IL6信号异常通过调节IL-6R/STAT3/miR-204-5p轴诱导结直肠癌耐药，该研究发现了结直肠癌微环境中免疫细胞和肿瘤细胞之间新的联系。

原始出处：

Yuan Yin,Surui Yao,et al.The Immune-microenvironment Confers Chemoresistance of Colorectal Cancer through Macrophage-Derived IL6.CLIN CANCER RES.December 2017 doi:10.1158/1078-0432.CCR-17-1283

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#插入话题

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2018-10-04 gwc392

#分泌#

23 0
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2017-12-12 kzlchina

#IL-6#

23 0
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2017-12-12 crystal0564

#结直肠#

34 0
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2017-12-10 zdvfsadb

学习啦

61 0
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2017-12-10 毛毛们

值得学习

72 0
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2017-12-10 1e1850b7m51(暂无匿称)

学习

66 0
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2017-12-10 1e14ffd0m25(暂无匿称)

学习学习

49 0

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