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.