title: Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma.
abstract: T-cell-mediated immunity has the ability to produce durable antimelanoma responses, resulting in improved survival of patients with advanced melanoma. Antigen presentation is a key determinant of 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 immunohistochemical analysis. GILT staining in melanocytes was observed in 70% of primary and 58% of metastatic melanomas versus 0% of nevi. When present, the GILT staining intensity in melanocytes was typically faint. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT staining in antigen-presenting cells (APCs) was detected in 100% of primary and metastatic melanomas versus 31% of nevi, and it was typically intense. GILT expression was increased in APCs of primary and metastatic melanomas compared with nevi, whereas MHC class II had equivalent high expression in APCs of all melanocytic lesions. GILT staining in keratinocytes was detected in 67% of primary melanomas versus 14% of nevi and 6% of metastatic melanomas. GILT, but not MHC class II, expression was increased in keratinocytes of primary melanomas compared with nevi and metastases. GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective antimelanoma T-cell responses. GILT expression may be a biomarker of immune recognition of melanoma.
authors.affiliation: aDepartment of Basic Medical Sciences, University of Arizona College of Medicine Phoenix, PhoenixbArizona Dermatopathology, ScottsdalecDivision of Epidemiology and Biostatistics, University of Arizona Mel and Enid Zuckerman College of Public HealthdVentana Medical Systems, Tucson, Arizona, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nguyen
authors.forename: Richard
authors.initials: R
authors.lastname: Bernert
authors.forename: Kevin
authors.initials: K
authors.lastname: In
authors.forename: Paul
authors.initials: P
authors.lastname: Kang
authors.forename: Noemi
authors.initials: N
authors.lastname: Sebastiao
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hu
authors.forename: K Taraszka
authors.initials: KT
authors.lastname: Hastings
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation
chemical_list: C056859:IFI30 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors