Gurrea-Rubio Mikel, Lin Feng, Wicha Max S, Mao-Draayer Yang, Fox David A
Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Department of Immunity and Inflammation, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States.
Front Immunol. 2025 Jan 7;15:1528478. doi: 10.3389/fimmu.2024.1528478. eCollection 2024.
Cluster of Differentiation 6 (CD6), an established marker of T cells, has multiple and complex functions in regulation of T cell activation and proliferation, and in adhesion of T cells to antigen-presenting cells and epithelial cells in various organs and tissues. Early studies on CD6 demonstrated its role in mediating cell-cell interactions through its first ligand to be identified, CD166/ALCAM. The observation of CD6-dependent functions of T cells that could not be explained by interactions with CD166/ALCAM led to discovery of a second ligand, CD318/CDCP1. An additional cell surface molecule (CD44) is being studied as a potential third ligand of CD6. CD166, CD318, and CD44 are widely expressed by both differentiated cancer cells and cancer stem-like cells, and the level of their expression generally correlates with poor prognosis and increased metastatic potential. Therefore, there has been an increased focus on understanding how CD6 interacts with its ligands in the context of cancer biology and cancer immunotherapy. In this review, we assess the roles of these CD6 ligands in both the pathogenesis and treatment of cancer.
分化簇6（CD6）是一种公认的T细胞标志物，在调节T细胞活化和增殖以及T细胞与各种器官和组织中的抗原呈递细胞和上皮细胞的黏附中具有多种复杂功能。早期对CD6的研究表明，它通过其首个被鉴定的配体CD166/活化白细胞黏附分子（ALCAM）介导细胞间相互作用。对T细胞依赖CD6的功能的观察，而这些功能无法通过与CD166/ALCAM的相互作用来解释，从而导致了第二种配体CD318/癌分化和趋化蛋白1（CDCP1）的发现。另一种细胞表面分子（CD44）正在作为CD6潜在的第三种配体进行研究。CD166、CD318和CD44在分化的癌细胞和癌干细胞样细胞中均广泛表达，它们的表达水平通常与不良预后和转移潜能增加相关。因此，人们越来越关注了解在癌症生物学和癌症免疫治疗背景下CD6如何与其配体相互作用。在这篇综述中，我们评估了这些CD6配体在癌症发病机制和治疗中的作用。
