Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas

William Vermi, Raffaella Bonecchi, Fabio Facchetti, Denise Bianchi, Silvano Sozzani, Silvana Festa, Angiola Berenzi, Marina Cella, Marco Colonna

Research output: Contribution to journalArticle

Abstract

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-α 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.

Original languageEnglish
Pages (from-to)255-268
Number of pages14
JournalJournal of Pathology
Volume200
Issue number2
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • Dendritic cells
  • Interferon-α
  • Melanoma
  • Plasmacytoid monocyte

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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