在肺癌中,加勒-3通过与TREM2的相互作用诱导致病性免疫抑制巨细胞
Qiaohua Wang1,2, Yongjian Wu1,3,4, Guanmin Jiang5
1Center for Infection and Immunity, Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
Journal of experimental & clinical cancer research : CR
|August 12, 2024
概括
这项研究揭示了加勒-3与瘤相关巨细胞 (TAMs) 上的骨髓细胞2 (TREM2) 上表达的触发受体相互作用. 抑制这种对可以通过恢复抗瘤免疫力来抑制肺癌的进展.
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:
- 瘤相关巨细胞 (TAMs) 的高透率促进瘤生长和免疫抑制.
- 在骨髓细胞2 (TREM2) 上表达的触发受体是TAM免疫抑制的关键调节者,但其招募和连接体相互作用仍然不清楚.
研究的目的:
- 阐明TREM2表达的TAMs的招募机制.
- 为了确定参与TAM介导免疫抑制的TREM2配体.
- 为了研究向肺癌中加勒-3/TREM2轴的治疗潜力.
主要方法:
- 流细胞计和单细胞RNA测序以分析TREM2表达.
- 质谱和免疫沉以确定TREM2结合蛋白.
- 试验室细胞和共同培养试验,体内小鼠模型 (TREM2条件淘汰,肺癌模型) 和药理学阻塞,以评估加勒-3/TREM2的功能和治疗疗效.
主要成果:
- 通过CCL2-CCR2轴招募TREM2+巨细胞.
- 加列-3作为TREM2连接体,损害了细胞形成并促进了TAM免疫抑制转化.
- 联合阻断TREM2和加勒-3显著抑制了肺癌的进展,并重塑了瘤的免疫微环境.
结论:
- 在肺癌TAM中确定了加勒-3和TREM2之间的新兴关联.
- 同时抑制加勒-3和TREM2为肺癌提供了一个有前途的治疗策略.
相关概念视频
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...