title: Expression of NK-associated receptors on cytotoxic T cells from melanoma patients: a two-edged sword?
abstract: The coexistence of tumor progression with a tumor-specific immune response constitutes a major paradox of tumor immunity. During the last decade, the presence of cytotoxic T lymphocytes (CTLs) recognising melanoma-associated antigens has been unequivocally demonstrated in numerous different in vivo and in vitro models. However, most often these melanoma-specific T lymphocytes do not control tumor growth. Several mechanisms that involve changes in melanoma phenotype and/or in T-cell differentiation and function could explain the inability of the immune response to control melanoma. In the last few years it has been demonstrated that cellular cytotoxicity is the result of a balance between activating signals triggered by the TCR and costimulatory molecules and inhibitory signals triggered by inhibitory receptors expressed by the CTL. Because the final outcome of the immune response against melanoma depends on the balance between activating and inhibitory signals, the expression de novo on melanoma cells of ligands for inhibitory NKRs and the down-regulation of costimulatory molecules may favor the escape of tumor cells from immunosurveillance. In this paper we review how altered expression of molecules required for T-cell costimulation could result in impaired lysis of melanoma. The modulation of antimelanoma T-cell responses by a group of receptors originally described on NK cells (NK-associated receptors) but which are now known also to be expressed on a subset of cytolytic effector cells is reviewed. We hypothesize that the expression of ligands for NKRs on melanoma cells may contribute to T-cell-mediated immune responses against melanoma either enhancing or inhibiting activation and differentiation to effector cells. Blocking inhibitory receptors or increasing activating receptors could result in new strategies to improve T-cell-mediated rejection of melanoma.
authors.affiliation: Department of Physiology, Immunology Unit, Veterinary Faculty, University of Extremadura, Cáceres, Spain. rtarazon@unex.es
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
authors.forename: Rocío
authors.initials: R
authors.lastname: Soto
authors.forename: Olga
authors.initials: O
authors.lastname: DelaRosa
authors.forename: Esther
authors.initials: E
authors.lastname: Peralbo
authors.forename: Luis
authors.initials: L
authors.lastname: Rioja
authors.forename: José
authors.initials: J
authors.lastname: Peña
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D002454:Cell Differentiation; D018450:Disease Progression; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins