肿瘤微环境中,GAS6/TAM 被持续激活,导致一系列免疫抑制信号的产生,如诱导肿瘤细胞表面的MHC-Ⅰ表达水平下降,引起肿瘤细胞中免疫检查点PD-L1表达升高,诱导分泌一些免疫抑制的细胞因子和趋化因子,如 TGF- β、TNF-α、IL-3、CCL-3 及 CXCL2 等,抑制宿主的抗肿瘤免疫应答,从而介导肿瘤的免疫逃逸。 GAS6/TAM信号...
针对GAS6/TAM上游信号的药物 由于下游的TAM受体在分布和功能上的差异,靶向位于信号通路上游的配体GAS6的优势在于能同时阻断三个受体信号通路的激活。目前开发的药物包括一些非TKI小分子化合物,阻断GAS6/TAM结合信号的GAS6单克隆抗体,以及通过合适蛋白工程组合而成的诱饵受体。在针对GAS6/TAM上游信号的药物开发中,进展...
因此,GAS6/TAM信号通路不仅在肿瘤发生、进展及转移中起到关键作用,同时也介导肿瘤的耐药及免疫逃逸,成为极具潜力的下一代肿瘤治疗靶点。AVB-500是一款对GAS6/TAM通路中配体GAS6进行高亲和力中和的诱饵融合蛋白,已获得大中华区肿瘤领域的独家开发和商业化权利。研究表明,GAS6/TAM通路与肿瘤免疫检查点...
Gas6/TAM参与炎性反应及其在矽尘致矽肺中作用 研究进展 宋菁 荣怿 崔秀青 陈卫红 矽尘(游离SiO:)是我国危害最严重的职业有害因素,长 期接触直接导致我国发病最高的职业病一尘肺,因此,矽尘及 其致病效应受到广泛重视。矽尘的致病机制一直未能阐明, 其引起免疫炎性反应被认为是其致病的起始【l_]1。生长停滞特 ...
TAM (TYRO3, AXL, and MERTK) protein tyrosine kinase membrane receptors and their vitamin K-dependent ligands GAS6 and protein S (PROS) are well-known players in tumor biology and autoimmune diseases. In contrast, TAM regulation of fibrogenesis and the inflammation mechanisms underlying metabolic ...
Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyt
Microglia and astrocytes are the main CNS glial cells responsible for the neuroinflammatory response, where they release a plethora of cytokines into the CNS inflammatory milieu. The TAM (Tyro3, Axl, Mer) receptors and their main ligand Gas6 are regulato
巨噬细胞通过其吞噬能力及分泌多种炎症因子对炎症反应发挥重要的调节作用,机体的免疫稳态依赖于炎症反应与负调控系统之间的相互调节.前期的研究主要集中在负调控系统如何抑制炎症反应上,本论文以小鼠腹腔巨噬细胞为研究对象,揭示了Toll样受体(TLRs)信号通路对负调控系统——Gas6/ProS-TAM的影响,及其对巨噬细胞分泌炎症...
4f, g); however, PROS transcription was not as much regulated as GAS6 by chemotherapeutics tested (Fig. 4h and Supplementary Fig. 6g). These data suggest that in Ewing sarcoma, chemotherapy provides both PtdSer and GAS6 (but not PROS) to activate TAM kinases. Fig. 4: Chemotherapy induces...