Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets.
Increased levels of interleukin (IL)-10 have been described as a negative prognostic indicator for survival in patients with various types of cancer. IL-10 exerts tolerogenic and immunosuppressive effects on dendritic cells, which are crucial for the induction of an antitumor immune response. Blood dendritic cell antigen (BDCA)-2 and BDCA-4 are specifically expressed by CD123(bright) CD11c- plasmacytoid dendritic cells; whereas BDCA-1 and BDCA-3 define 2 distinct subsets of CD11c+ myeloid dendritic cells. In this study, the T-helper cell (Th)1/Th2 cytokine serum profile of 65 hepatocellular carcinoma patients was assessed. We found that serum levels of IL-10 were substantially increased in hepatocellular carcinoma patients as compared with controls. Peripheral blood mononuclear cells from healthy volunteers were exposed to recombinant human (rh)IL-10 in vitro to additionally characterize its impact on distinct blood dendritic cell subsets. A dramatic decrease of all myeloid dendritic cell (MDC) and plasmacytoid dendritic cell (PDC) subsets was detectable after 24 hours of continuous rhIL-10 exposure. Moreover, the expression of HLA-DR, CD80 and CD86, was significantly reduced on rhIL-10-treated dendritic cell subsets. Direct ex vivo flow cytometric analysis of various dendritic cell subpopulations in peripheral blood from hepatocellular carcinoma patients revealed an immature phenotype and a substantial reduction of circulating dendritic cells that was associated with increased IL-10 concentrations in serum and with tumor progression. These findings confirm a predominantly immunosuppressive role of IL-10 for circulating dendritic cells in patients with hepatocellular carcinoma and, thus, may indicate novel aspects of tumor immune evasion.
Beckebaum
Susanne
S
Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany. susanne.beckebaum@uni-essen.de
Zhang
Xia
X
Chen
Xiao
X
Yu
Zhengya
Z
Frilling
Andrea
A
Dworacki
Grzegorz
G
Grosse-Wilde
Hans
H
Broelsch
Christoph Erich
CE
Gerken
Guido
G
Cicinnati
Vito R
VR
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D039521:CD11c Antigen / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D045744:Cell Line, Tumor; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D010641:Phenotype; D011971:Receptors, Immunologic; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; C497964:CD86 protein, human; C443299:CLEC4C protein, human; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016753:Interleukin-10