Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer.

TONYA WEBB; XIANGMING LI; ROBERT GIUNTOLI; PABLO HECTOR HORACIO LOPEZ; CHRISTOPH HEUSER; RONALD L. SCHNAAR; MORIYA TSUJI; CHRISTIAN KURTS; MATHIAS OELKE; JONATHAN SCHNECK

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia; Año: 2012 vol. 72 p. 3744 - 3752

0008-5472

Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion.