Potential Roles of Human Chorionic Gonadotropin in Tumorigenesis and the Development of Novel Vaccination Strategies (P2116)

Abstract Human chorionic gonadotropin (hCG) is associated with poor prognosis in several cancers, but causative molecular events remain inadequately described. In this study, tumor cells were found to express message for both hormonal subunits. Along with increasing cell viability, exogenous hCG enhanced several key tumor-promoting mechanisms. It induced the transcriptional activation and secretion of the angiogenic factors VEGF and IL8. Matrix-degrading enzymes associated with invasion (MMP2 and MMP9) were also enhanced, as was invasiveness. hCG up-modulated secretion of the proteoglycan versican and the consequent secretion of the inflammatory cytokines IL6 and TNFα from macrophages. hCG up-regulated FOXP3 in tumor cells, leading to the increased secretion of the immunosuppressive cytokines IL10 and TGFβ and up-modulation of CTLA-4; co-culture hCG-stimulated tumor cells with mature BMDCs heightened the secretion of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase. Anti-hCG antibodies restricted the growth of human tumor xenografts, and immunization with a novel anti-hCG vaccine formulation (βhCG-TT + Mycobacterium indicus pranii) synergistically attenuated tumor development and prolonged survival in syngeneic mice. By preventing autocrine and subsidiary paracrine hCG-induced effects on multiple pathways, new generation anti-hCG vaccines may therefore hold considerable promise as adjunct therapy in patients of gonadotropin-sensitive tumors.