库尔库明通过调节癌症相关纤维细胞衍生的外体miRNA-146aa调节树突细胞成熟
Sheefa Mirza1,2,3, Clement Penny1, Nayan K Jain2
1Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Journal of cancer research and therapeutics
|February 22, 2024
概括
与癌症相关的纤维细胞 (CAFs) 产生调节性树突细胞 (DCs),抑制免疫反应. 黄可以扭转这种情况,促进成熟的DC,并通过调节瘤微环境 (TME) 来增强抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
背景情况:
- 癌症相关纤维细胞 (CAF) 是瘤微环境 (TME) 的关键组成部分,通过分泌因素影响免疫反应.
- 对CAFs对树突细胞 (DC) 成熟和功能的具体影响仍然不完全理解.
研究的目的:
- 研究肺CAF衍生的外体和细胞因子对DC成熟的作用.
- 评估黄素在TME内调节DC成熟的免疫调节潜力.
主要方法:
- 未成熟的DCs (imDCs) 用CAFs-条件介质 (CAFs-CM) 进行培养,通过qRT-PCR评估DC成熟标志物 (CD80,CD83,CD86,CTLA4).
- 使用ELISA分析了CAF-CM中的表观遗传调节剂 (miRNAs:miR-221,miR-222,miR-155,miR-142-3p,miR-146a) 和细胞因子.
- 还评估了黄素对CAFs-CM治疗的DCs的影响.
主要成果:
- CAFs-CM诱导的调节性DCs具有降低的成熟标志物和增加的miR-146a表达.
- 这些调节性DCs表现出高的抗炎细胞因子 (IL-6,IL-10,TGF-β) 和降低TNF-α.
- 黄素治疗使调节性DC转向成熟的DC (mDC),增强了共刺激分子和降低了免疫抑制因素和miR-146a.
结论:
- 肺CAFs通过特定的miRNA和细胞因子促进DC不成熟和免疫抑制.
- 黄素有效地逆转CAF介导的DC抑制,促进抗瘤免疫力.
- 这些发现突显了黄素在基于DC的癌症免疫疗法中的潜力,通过向CAF和TME.
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