title: The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors.
abstract: Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.
authors.affiliation: Department of Immunology, Division of Investigative Science, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
authors.forename: M
authors.initials: M
authors.lastname: Bower
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: A
authors.initials: A
authors.lastname: Wildfire
authors.forename: H
authors.initials: H
authors.lastname: Pandha
authors.forename: A
authors.initials: A
authors.lastname: Dalgleish
authors.forename: J
authors.initials: J
authors.lastname: Spicer
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D006360:Heat-Shock Proteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008207:Lymphatic Metastasis / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008545:Melanoma / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006360:Heat-Shock Proteins; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1