通过激活CXCLs/CXCR2轴的NKX2-1抑制招募的中性粒细胞促进肺腺癌的进展
Anita S La'ah1,2, Ping-Hsing Tsai2,3, Aliaksandr A Yarmishyn2
1Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, 115, Taiwan.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 8, 2024
概括
肺腺癌中NK2本体盒1 (NKX2-1) 的下调促进了通过CXCLs/CXCR2信号传导的中性粒细胞透,推动了瘤的生长. 抑制CXCR2为NKX2-1低瘤提供了潜在的治疗方法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- NK2本体箱1 (NKX2-1) 是肺腺癌 (LUAD) 进展的一个关键标志物.
- 瘤免疫微环境通过对膜信号影响LUAD的推进.
- 在塑造瘤免疫微环境中的NKX2-1的作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究NKX2-1在调节LUAD中的瘤免疫微环境中的作用.
- 阐明NKX2-1影响中性粒细胞招募和LUAD进展的机制.
- 探索向NKX2-1低LUAD中已识别的途径的治疗潜力.
主要方法:
- 单细胞RNA测序和Visium in situ杂交,以分析瘤免疫透.
- 基因表达分析 (qRT-PCR,化学激素阵列) 用于量化化学激素分泌.
- ATAC-seq研究NKX2-1对化学基因基因促进者的调节作用.
- 在体内研究中使用了正位体综原性瘤模型和CXCR2抗剂治疗.
主要成果:
- 在高度的LUAD中,NKX2-1的下调,与增加的中性粒细胞透相关.
- 在LUAD细胞中NKX2-1的枯竭可提高CXCL1,CXCL2,CXCL3和CXCL5的表达和分泌.
- NKX2-1限制了CXCL1,CXCL2和CXCL5基因的促进体活性.
- 用SB225002抑制CXCR2信号,在NKX2-1低的模型中降低了瘤生长.
结论:
- NKX2-1对CXCL化学基因的表达进行负调节,从而通过CXCLs/CXCR2轴控制中性粒细胞透.
- 低调NKX2-1促进瘤促进中性粒细胞的招募,有助于LUAD的进展.
- 向CXCR2为低NKX2-1表达的LUAD患者提供了一个有前途的治疗策略.
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