GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition

Abstract

Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma.