The immunomodulating roles of glycoproteins in epithelial ovarian cancer

Abstract

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. KeywordsGlycoproteins; T cells; NK cells; Epithelia Ovarian Cancer; MUC16; Glycodelin; MUC1; Mucins; Immune Synapse; Review INTRODUCTIONOvarian cancer is a highly insidious disease that is usually detected at a very late stage when the possibility of an efficient therapeutic management of the cancer is relatively low (1-3). Therefore, in most women with advanced ovarian cancer the five year survival rate is around 30-55% (4). Specific biomarkers that can detect the cancer at an early stage (when the survival rate after treatment is 80%) are not available (5,6). In women with advanced disease, the standard of care includes an initial surgical debulking of the tumor followed by an intense chemotherapy with platinum or taxol based compounds. Under these treatment conditions the cancer regresses and the low level of the tumor is monitored by measuring the Send correspondence to: Manish S. Patankar, Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 600 Highland Avenue, H4/657 CSC, Madison, patankar@wisc.edu. NIH Public Access Author ManuscriptFront Biosci (Elite Ed). Author manuscript; available in PMC 2015 February 12. Published in final edited form as:Front Biosci (Elite Ed). ; 4: 631-650. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript serum concentration of the biomarker CA125 (7-10). A steady elevation in serum CA125 levels from this nadir is indicative of recurrent disease (10).The progression of ovarian cancer requires the cancer cells to first develop on the surface of the ovary or along the walls of the fallopian tubes and then metastasize to other sites within the peritoneum (11)(12)(13)(14)(15)(16)(17)(18). Starting with the initiation of the cancer to metastasis, the tumor cells encounter distinct immunologic environments and therefore have to adapt at each site to not only overcome immune recognition but al...