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Cancer Res. 2012 Aug 1;72(15):3744-52. doi: 10.1158/0008-5472.CAN-11-2695. Epub 2012 May 30.

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

Author information

1
Department of Pathology and The Kelly Gynecologic Oncology Service, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21201, USA. twebb@som.umaryland.edu

Abstract

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.

PMID:
22649190
PMCID:
PMC3438513
DOI:
10.1158/0008-5472.CAN-11-2695
[Indexed for MEDLINE]
Free PMC Article

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