[Frontiers in Bioscience E4, 631-650, January 1, 2012]

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

Manish S. Patankar1, Jennifer A.A. Gubbels2, Mildred Felder1, Joseph P. Connor1

1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, WI-53792-6188, 2Department of Biology, Augustana College, Sioux Falls SD

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Immune surveillance and immune editing
4. Immune environment in ovarian cancer
5. Anti-tumor immune response
6. The decision to kill
7. Glycoproteins and immune protection
7.1. Glycoprotein shield
7.2. Immunomodulation via interaction of immune receptors with carbohydrate ligands
7.2.1. Ovarian tumor glycome
7.2.2. Tn and Sialyl Tn antigens
7.2.3. Thomsen-Friedenrich (T or Tf) antigen
7.2.4. LacDiNAc glycans
7.2.5. Bisecting-type N-linked glycans
7.2.6. Sialylated N-linked or O-linked glycans
7.3. Cytokine binding to glycoprotein
7.4. Aberrant glycosylation and the autoantibody response
8. Conclusions
9. Perspective
10. Acknowledgements
11. References

1. 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.