Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma (TUM2P.1038)

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Abstract T cell-mediated immunity has the ability to produce durable anti-melanoma responses resulting in improved survival of patients with advanced melanoma. Antigen presentation in the tumor microenvironment directs anti-melanoma T cell responses. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens to CD4+ T cells. However, GILT expression in melanoma has not been defined. We evaluated GILT and MHC class II expression in human primary and metastatic melanomas and nevi using immunohistochemistry. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT expression was increased in antigen presenting cells of primary and metastatic melanomas compared to nevi, whereas MHC class II had equivalent high expression in antigen presenting cells of all melanocytic lesions. Keratinocytes in primary melanoma lesions had increased GILT and MHC class II expression compared with nevi. Increased GILT expression in melanocytes, antigen presenting cells and keratinocytes of melanoma demonstrates that changes in the antigen presentation pathway occur in the tumor microenvironment. GILT expression in melanoma is anticipated to result in improved presentation of melanoma antigens and more effective anti-melanoma T cell responses and may be a biomarker of immune recognition of melanoma.