在巨细胞上,A2AR介导的CXCL5上调促进通过NETosis通过NSCLC的进展
Qingyang Lei1,2,3, Shanshan Zhen1,2,3, Lei Zhang4
1Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, Henan, China.
Cancer immunology, immunotherapy : CII
|April 20, 2024
概括
与瘤相关的巨细胞 (TAMs) 通过通过腺素信号传导调高CXCL5,从而导致T细胞功能障碍,推动非小细胞肺癌 (NSCLC) 的进展. 抑制A2AR可能会恢复抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 创造了一个免疫抑制的瘤微环境.
- 由TAM驱动的瘤进展和免疫抑制的机制需要进一步阐明.
研究的目的:
- 为了研究巨细胞和非小细胞肺癌 (NSCLC) 细胞之间的交叉声.
- 确定TAMs促进瘤进展和免疫逃避的分子机制.
主要方法:
- 建立了巨细胞和NSCLC细胞的体外共同培养模型.
- 利用分子生物学技术分析信号通路,包括腺受体A2AR,CD39,CD73和NFκB.
- 评估中性粒细胞外细胞陷 (NET) 的形成及其对CD8+T细胞功能的影响.
主要成果:
- 在巨细胞中A2AR的腺素刺激通过NFκB信号传递对CXCL5进行上调.
- 在中性粒细胞中,CXCL5诱导了NETosis,导致CD8+ T细胞耗尽和效应器功能受损.
- 抑制A2AR逆转了CXCL5上调,减少了中性粒细胞透,并缓解了CD8+ T细胞功能障碍.
结论:
- 确定了一种涉及腺-A2AR-CXCL5-中性粒细胞的新途径,该途径促进NSCLC的免疫逃避.
- 向腺-A2AR通路提供了一个潜在的治疗策略,以恢复NSCLC的抗瘤免疫力.
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