Targeted attack: mechanisms by which ovarian cancers suppress the immune system

Irina V. Tiper, Tonya J. Webb


Epithelial ovarian cancer (EOC) is the seventh most common cancer diagnosis among women worldwide and has the highest mortality rate of all gynecologic malignancies (1). In the United States, EOC is the fifth most common cause of cancer deaths among women (2). Despite improvements in treatment, 5-year survival rates of patients with advanced ovarian cancer remain less than 50% (3,4) because the majority of patients present with late stage disease (5). Thus, the identification of novel biomarkers and the development of innovative therapeutic approaches are urgently needed. It has been well established that evading immune surveillance is critical for tumor growth and metastasis, and other groups have shown that vascular endothelial growth factor (VEGF) expression is inversely correlated with survival in ovarian cancer patients (6,7). Therefore, we investigated the effects of ovarian cancer-associated VEGF on CD1d-mediated antigen presentation to natural killer T (NKT) cells (8). We found that inhibition of VEGF production by ovarian cancer cell lines led to a reduction in the expression of the immunosuppressive ganglioside GD3 and restored NKT cell activation. Thus, we identified a novel link between immunosuppressive ganglioside shedding and VEGF production by ovarian cancers.