乳酸受体GPR81对乳腺癌免疫微环境的增强作用
Shenchao Guo1,2, Jianliang Zhou1, Pengrong Lou1
1Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Ningbo University, Ningbo, People's Republic of China.
Molecular carcinogenesis
|May 30, 2023
概括
G蛋白结合受体 (GPR81) 可能有助于三阴性乳腺癌 (TNBC) 逃避免疫检测. 激活GPR81降低PD-L1,可能在某些乳腺癌中增强抗瘤免疫力.
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:
- G蛋白结合受体 (GPR81) 作为乳酸受体,在免疫调节中出现.
- 它在瘤免疫逃避中的确切作用,特别是在乳腺癌中,仍然不完全理解.
研究的目的:
- 研究GPR81激活对三阴性乳腺癌 (TNBC) 细胞和巨细胞的影响.
- 使用TCGA数据分析GPR81表达模式及其与乳腺癌免疫透的相关性.
主要方法:
- 对GPR81表达和免疫透相关性的TCGA数据库分析.
- 流细胞计和ELISA用于评估免疫检查点和细胞因子水平.
- 在体外实验中,涉及GPR81激动剂治疗和siRNA在TNBC和巨细胞系中的淘汰.
主要成果:
- 与正常乳腺组织相比,GPR81表达在乳腺癌 (BRCA) 中显著下降,特别是在基底类型的亚型中.
- 刺激GPR81抑制了特定TNBC细胞系 (BT-549,MDA-MB-231) 中的PD-L1表达,这种效应被GPR81淘汰扭转.
- 激活GPR81对PMA诱导的THP-1细胞中PD-L1表达的影响很小,对细胞因子分泌没有显著影响.
结论:
- 通过降低PD-L1表达的调节,GPR81可能会促进糖性TNBC中的免疫监测.
- 向GPR81为乳腺癌提供了潜在的治疗策略,特别是用于增强抗瘤免疫反应.
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