Insights into the Role of GILT in HLA Class II Antigen Processing and Presentation by Melanoma

Metastatic melanoma is one of the deadliest of skin cancers and is increasing in incidence. Since current treatment regimens are ineffective at controlling and/or curing the disease, novel approaches, such as immunotherapy, for treating this malignant disease are being explored. In this review, we discuss potential melanoma antigens (Ags) and their role in utilizing the HLA class II pathway to elicit tumor Ag-specific CD4+ T cell responses in order to effectively induce long-lasting CD8+ antitumor memory. We also discuss the role of endolysosomal cathepsins and Gamma-Interferon-inducible Lysosomal Thiol reductase (GILT) in Ag processing and presentation, and at enhancing CD4+ T cell recognition of melanoma cells. This review also summarizes our current knowledge on GILT and highlights a novel mechanism of GILT-mediated immune responses against melanoma cells. At the end, we propose a strategy employing GILT in the development of a potential whole cell vaccine for combating metastatic melanoma.