title: Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival.
abstract: Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma.
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Potrony
authors.affiliation: Grup D'Immunoreceptors Del Sistema Innat I Adaptatiu, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Grup D'Immunoreceptors Del Sistema Innat I Adaptatiu, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium, Heidelberg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Melanoma Unit, Molecular Biology and Genetics Department, Hospital Clínic De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Joan-Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Martí
authors.affiliation: Grup D'Immunoreceptors Del Sistema Innat I Adaptatiu, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Armiger
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium, Heidelberg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Pol
authors.initials: P
authors.lastname: Giménez-Xavier
authors.affiliation: Grup D'Immunoreceptors Del Sistema Innat I Adaptatiu, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Martínez-Florensa
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.|Centro De Investigación Biomédica En Red En Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
authors.affiliation: Grup D'Immunoreceptors Del Sistema Innat I Adaptatiu, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.|Department of Immunology, Hospital Clínic De Barcelona, Barcelona, Spain.|Department of Cell Biology, Immunology and Neurosciences, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000328:Adult; D018956:CD5 Antigens / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018956:CD5 Antigens