Interferon-gamma-induced ICAM-1 and CD40 expression, complete lack of HLA-DR and CD80 (B7.1), and inconsistent HLA-ABC expression in basal cell carcinoma: a possible role for interleukin-10?
Basal cell carcinomas (BCCs) of the skin show varying degrees of peritumoural inflammatory infiltrate consisting mainly of T cells, but lack an effective T-cell-mediated immune response. This may be caused by the absence of the major histocompatibility complex (MHC) class I and II antigens, intercellular adhesion molecule-1 (ICAM-1), CD40 and CD80 (B7.1). Interferon-gamma (IFN-gamma) is known to induce or up-regulate their expression on epithelial cells, whereas interleukin-10 (IL-10) down-regulates their expression. The induction and up-regulation of HLA-ABC, HLA-DR, ICAM-1, CD40, and CD80 in BCC and normal skin from BCC patients were investigated in a culture system using recombinant human IFN-gamma (rHuIFN-gamma). The levels of IL-10 were determined in the supernatants after culture. The results showed that only ICAM-1 expression was significantly up-regulated on BCC cells. However, in the normal epidermis of BCC patients and in the epidermis overlying the tumour nests, significant up-regulation of ICAM-1, and CD40, and CD80 and slight up-regulation of HLA-DR were observed. No changes in HLA-ABC expression were observed in either normal skin or BCC. High levels of IL-10 were present in the supernatants of BCC biopsies after culture. It may be concluded that it is highly likely that the presence of IL-10 in BCC is directly or indirectly responsible for the complete lack of expression of HLA-DR, ICAM-1, CD40 and CD80 and the inconsistent expression of HLA-ABC on BCC cells in situ and may be a way of escaping immune survillance.
Department of Dermato-Venereology, Erasmus University Rotterdam, The Netherlands.
A J
AJ
Kooy
E P
EP
Prens
A
A
Van Heukelum
V D
VD
Vuzevski
T
T
Van Joost
B
B
Tank
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019013:CD40 Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma