Presence and maturity of dendritic cells in melanoma lymph node metastases.
Immune avoidance mechanisms play a key role in the successful dissemination of melanoma. One mechanism whereby this could be achieved is by interfering with dendritic cell (DC) presentation of tumour-associated antigens to naïve T cells. In particular, immature DCs characterized by the absence of accessory molecules are known to be immunosuppressive and to be involved in the induction of tolerance. The present study has investigated the presence and activation status of DCs within melanoma metastases in the regional lymph nodes. Using image analysis techniques, the expression of Factor XIIIa (FXIIIa), CD40, CD83 and HLA-DR and the morphological features of DCs were examined in paraffin sections from 26 lymph nodes containing melanoma metastases. DCs expressing FXIIIa were found in 70% of the lymph nodes. The number of DCs identified was generally small but there were more concentrated areas of DCs designated as hotspots. In these areas of high FXIIIa staining, the percentage area occupied by DCs varied between 0.1% and 10%. The majority of FXIIIa-positive cells did not express the DC maturation markers CD83 or CD40 and morphologically were rounded with few dendrites, indicating that they were immature. The cells did, however, express high levels of HLA-DR, suggesting that they have the ability to present antigen but lack the accessory molecules required to initiate an immune response. Immature DCs, characterized by phenotypic and morphological features, are therefore present within the tumour deposits in lymph nodes infiltrated by melanoma and may specifically modulate the anti-melanoma immune response.
Polak
Marta E
ME
Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth, UK. marta.polak@porthosp.nhs.uk
Johnson
Penny
P
Di Palma
Silvana
S
Higgins
Bernie
B
Hurren
Jeremy
J
Borthwick
Nicola J
NJ
Jager
Martine J
MJ
Mccormick
Deirdre
D
Cree
Ian A
IA
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D026122:Factor XIIIa / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007136:Immunoglobulins / Q000378:metabolism; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000276:immunology / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D019013:CD40 Antigens; D026122:Factor XIIIa; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen