Patankar Manish S, Gubbels Jennifer A A, Felder Mildred, Connor Joseph P
Department of Obstetrics and Gynecology, University of Wisconsin-Madison, WI 53792-6188, USA.
Front Biosci (Elite Ed). 2012 Jan 1;4(2):631-50. doi: 10.2741/405.
The complexity of the immune system demands an intricate defense mechanism by tumors. Ovarian and other tumors employ specific glycoproteins and the associated glycan sequences to modulate immune responses. Glycoproteins enable tumor cells that express or secrete these molecules to evade immune cell attack and induce the immune system to promote tumor growth. This review focuses first on the immune environment in ovarian cancer, and the mechanisms of activation and inhibition that immune cells undergo in order to either attack or ignore a target cell. Next we illustrate the immunomodulatory roles of ovarian cancer-associated glycans and glycoproteins in 1. preventing immune synapse formation, 2. serving as ligands of immune cell receptors, 3. scavenging cytokines and chemokines, and 4. participating in the formation of autoantibodies against the tumor. The importance of these immunomodulating strategies from the view points of understanding the tumor immunology of ovarian tumors, potential origin of such mechanisms, and specific strategies to circumvent the glycoconjugate-mediated suppression of immune responses is discussed in this review.
免疫系统的复杂性要求肿瘤具备复杂的防御机制。卵巢癌及其他肿瘤利用特定的糖蛋白及相关聚糖序列来调节免疫反应。糖蛋白使表达或分泌这些分子的肿瘤细胞能够逃避免疫细胞的攻击,并诱导免疫系统促进肿瘤生长。本综述首先聚焦于卵巢癌中的免疫环境,以及免疫细胞为攻击或忽略靶细胞而经历的激活和抑制机制。接下来,我们阐述卵巢癌相关聚糖和糖蛋白在以下方面的免疫调节作用:1. 阻止免疫突触形成;2. 作为免疫细胞受体的配体;3. 清除细胞因子和趋化因子;4. 参与针对肿瘤的自身抗体形成。本综述从理解卵巢肿瘤的肿瘤免疫学、此类机制的潜在起源以及规避糖缀合物介导的免疫反应抑制的具体策略等角度,探讨了这些免疫调节策略的重要性。