Abstract 4787: GILT regulates antigen processing and CD4+ T cell recognition of melanoma cells

Abstract

Abstract Metastatic melanoma is one of the deadliest of skin cancers and is increasing in incidence. Since current treatment regimens are ineffective at curing the disease, novel approaches, such as immunotherapy, for treating this malignant disease are being explored to elicit long-lasting antitumor immunity. We have previously shown that the majority of metastatic melanoma cells express HLA class II molecules, but lack Gamma-Interferon-inducible Lysosomal Thiol reductase (GILT), which differentially regulates HLA class II-restricted antigen processing and presentation. The purpose of this study was to investigate the mechanisms by which GILT insertion influences CD4+ T cells recognition of human melanoma cells via the HLA class II pathway. Biochemical analysis of melanoma cells showed that GILT expression upregulated the HLA class II components such as HLA-DM and invariant chain while class II protein expression remained unchanged. An increase in endolysosomal cathepsin protein expression and activity was also observed in melanoma cells transfected with GILT. Data obtained from biochemical and functional assays suggest that GILT insertion may help melanoma cells generate more antigenic determinants that are readily accessible to class II loading and presentation to CD4+ T cells. Taken together, these data suggest that GILT-inserted melanoma cells could be used in the design of whole cell vaccines for the treatment of metastatic melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4787.