通过SYK:功能和生物信息学见解,SIRPB1通过SYK调节质瘤微环境中的炎症因子表达:功能和生物信息学见解
Ren Geng1, Yao Zhao1, Wanzhen Xu2
1Department of Neurosurgery, First Hospital of Jilin University, No. 1, Xinmin Street, Chaoyang District, Changchun, China.
Journal of translational medicine
|April 9, 2024
概括
质瘤中SIRPB1的上调,对免疫微环境和患者的存活率产生负面影响. 向SIRPB1可能为质瘤治疗提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 质瘤中SIRPB1表达升高,促进瘤的进展.
- 它在质瘤免疫微环境中的确切作用在很大程度上仍未被描述.
研究的目的:
- 研究SIRPB1表达与质瘤临床病理特征之间的关系.
- 阐明SIRPB1在质瘤免疫环境中的功能.
- 开发基于SIRPB1表达的质瘤预后模型.
主要方法:
- 分析了1152个正常 (GTEx) 和670个质瘤 (TCGA) 样本.
- 在THP-1细胞中SIRPB1的CRISPR/Cas9基因淘汰,用于用巨细胞和质瘤细胞进行体外共培研究.
- 建立一个包括SIRPB1表达和临床病理变量在内的预后名录.
主要成果:
- 质瘤的SIRPB1水平显著更高,与较差的免疫微环境和患者存活率降低相关.
- 激活SIRPB1触发SYK酸化和下游信号 (,MAPK,NF-κB) 主要发生在髓状细胞中.
- 巨细胞中SIRPB1淘汰会减少关键细胞因子 (IL1RA,CCL2,IL-8),这些细胞因子通过SIRPB1再表达而恢复,但被SYK抑制剂抑制.
- 增加的SIRPB1表达与较低的整体存活率有关键联系,预测性名谱显示出高准确性.
结论:
- 瘤细胞通过SIRPB1被巨细胞激活,导致TME重编程.
- SIRPB1代表了质瘤治疗的潜在治疗点.
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