Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Clin Immunol. 2012 Feb;142(2):107-16. doi: 10.1016/j.clim.2011.09.011. Epub 2011 Oct 6.
Galectin-1 (Gal-1) is one of 15 evolutionarily conserved ß-galactoside-binding proteins that display biologically-diverse activities in pathogenesis of inflammation and cancer. Gal-1 is variably expressed on immune cells and endothelial cells, though is commonly found and secreted at high levels in cancer cells. It induces apoptosis in effector T cells through homodimeric binding of N-acetyllactosamines on membrane glycoproteins (Gal-1 ligands). There is also compelling evidence in models of cancer and autoimmunity that recombinant Gal-1 (rGal-1) can potentiate immunoregulatory function of T cells. Here, we review Gal-1's structural and functional features, while analyzing potential drawbacks and technical difficulties inherent to rGal-1's nature. We also describe new Gal-1 preparations that exhibit dimeric stability and functional activity on T cells, providing renewed excitement for studying Gal-1 efficacy and/or use as anti-inflammatory therapeutics. We lastly summarize strategies targeting the Gal-1-Gal-1 ligand axis to circumvent Gal-1-driven immune escape in cancer and boost anti-tumor immunity.
半乳糖凝集素-1(Gal-1)是 15 种进化上保守的β-半乳糖苷结合蛋白之一,在炎症和癌症发病机制中具有多种生物学活性。Gal-1 在免疫细胞和内皮细胞上的表达不同,但在癌细胞中通常以高水平普遍存在和分泌。它通过膜糖蛋白上 N-乙酰乳糖胺(Gal-1 配体)的同源二聚体结合诱导效应 T 细胞凋亡。在癌症和自身免疫模型中也有确凿的证据表明,重组 Gal-1(rGal-1)可以增强 T 细胞的免疫调节功能。在这里,我们综述了 Gal-1 的结构和功能特征,同时分析了 rGal-1 性质所固有的潜在缺点和技术困难。我们还描述了新的 Gal-1 制剂,它们在 T 细胞上表现出二聚体稳定性和功能活性,为研究 Gal-1 的疗效和/或用作抗炎治疗药物提供了新的动力。最后,我们总结了靶向 Gal-1-Gal-1 配体轴的策略,以规避 Gal-1 驱动的癌症免疫逃逸,并增强抗肿瘤免疫。