title: Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor.
abstract: As the most potent antigen presenting cells, dendritic cells (DCs) play key roles in the immune response against tumors. Their density in the tumor tissue has been associated with prognosis in patients with various cancers. However, few studies have been aimed at the presence and maturation state of DCs in cutaneous melanoma, with regard to their potential clinical correlates. In this study, the density of DCs expressing CD1a and the maturation marker DC-LAMP was determined by immunohistochemistry in primary tumor samples from 82 patients with cutaneous malignant melanoma. Intratumoral and peritumoral cell densities were analyzed in relation to tumor thickness and the subsequent development of metastases, as well as to patients' survival. CD1a(+) DCs were found both infiltrating melanoma cell nests and in the surrounding stroma, while DC-LAMP(+) mature DCs were generally confined to the peritumoral areas, associated with lymphocytic infiltrates. DC density values significantly correlated with the number of activated (CD25(+) or OX40(+)) T lymphocytes (p < 0.001). The degree of infiltration by CD1a(+) and DC-LAMP(+) DCs showed strong inverse correlation with the thickness of melanomas (p < 0.001). High peritumoral density of mature DCs was associated with significantly longer survival (p = 0.0195), while density of CD1a(+) cells had a prognostic impact of borderline significance (p = 0.0610). Moreover, combination of high peritumoral CD1a(+) or DC-LAMP(+) cell density with high number of CD25(+) or OX40(+) lymphocytes identified patient subgroups with more favorable survival compared to other subgroups. A multivariate survival analysis involving DC and activated T-cell densities alone and in combinations, as well as traditional prognostic factors, identified high DC-LAMP(+) cell/high OX40(+) cell density and Breslow index as independent predictors of good prognosis. These results suggest that the presence of CD1a(+) DCs primarily depends on the thickness of melanomas, without direct relationship with the patients' survival. On the other hand, the density of mature DCs, especially in association with that of activated T cells, proved of prognostic importance, suggesting that these parameters could be considered as signs of a functional immune response associated with better outcome of the disease.
authors.affiliation: Department of Tumor Progression, National Institute of Oncology, 7-9 Ráth György u., Budapest, H-1122, Hungary. ladanyi@oncol.hu
authors.forename: Andrea
authors.initials: A
authors.lastname: Ladányi
authors.forename: Judit
authors.initials: J
authors.lastname: Kiss
authors.forename: Beáta
authors.initials: B
authors.lastname: Somlai
authors.forename: Katalin
authors.initials: K
authors.lastname: Gilde
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fejos
authors.forename: Anita
authors.initials: A
authors.lastname: Mohos
authors.forename: István
authors.initials: I
authors.lastname: Gaudi
authors.forename: József
authors.initials: J
authors.lastname: Tímár
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000276:immunology*; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000276:immunology*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D014408:Biomarkers, Tumor; D051907:Lysosomal Membrane Proteins