Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas.
The present study has analysed the distribution and phenotype of dendritic cells (DCs) in primary cutaneous melanomas and sentinel lymph nodes by immunohistochemistry. In primary melanomas, an increase of DCs was found in the epidermis and the peritumoural area. Intraepidermal DCs were mostly CD1a(+)/Langerin(+) Langerhans cells. Peritumoural DCs included a large population of DC-SIGN(+)/mannose-receptor(+)/CD1a(-) DCs, a small subset of CD1a(+) DCs, and, remarkably, plasmacytoid monocytes/plasmacytoid DCs (PM/PDCs). The PM/PDCs, most likely recruited by SDF-1 secreted by melanoma cells, produced type I interferon (IFN-I), but the expression of the IFN-alpha inducible protein MxA was extremely variable and very limited in the majority of cases. All DC subsets were predominantly immature. The peritumoural area also contained a minor subset of mature CD1a(+) DCs. However, the small amount of local interleukin (IL)-12 p40 mRNA and the naïve phenotype of 20-50% of peritumoural T-lymphocytes are consistent with poor T-cell stimulation or erroneous recruitment. In sentinel lymph nodes, notable expansion of mature CD1a(+)/Langerin(+) DCs was observed. The paucity of intratumoural DCs and the predominant immature phenotype of peritumoural dermal DCs indicate defective maturation of primary cutaneous melanoma-associated DCs, resulting in lack of T-cell priming. These results may explain why melanoma cells grow despite the presence of infiltrating immune cells.
Vermi
William
W
Department of Pathology, University of Brescia, Brescia, 25124 Brescia, Italy.
Bonecchi
Raffaella
R
Facchetti
Fabio
F
Bianchi
Denise
D
Sozzani
Silvano
S
Festa
Silvana
S
Berenzi
Angiola
A
Cella
Marina
M
Colonna
Marco
M
D000368:Aged; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018664:Interleukin-12