Decreased function of peripheral blood dendritic cells in patients with hepatocellular carcinoma with hepatitis B and C virus infection.
BACKGROUND
Tumour immunity does not seem to be induced effectively in tumour-bearing hosts, including in patients with hepatocellular carcinoma (HCC). One possible reason is that function of dendritic cells (DC) is decreased in such hosts.


METHODS
We evaluated T cell stimulatory activity and interleukin (IL)-12 production of DC and interferon (IFN)-gamma and IL-10 production of T cells of peripheral blood from 12 control individuals and 21 patients with chronic hepatitis C virus (HCV) infection (six with chronic hepatitis (CH), eight with liver cirrhosis (LC) and 13 with HCC). Five hepatitis B virus (HBV)-infected patients with HCC were included as a disease control group. The DC were prepared by the culture of T cell-depleted populations of peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony stimulating factor and IL-4 for a total of 11-12 days. The cytokine levels were assayed by ELISA. To test the stimulatory function of DC in T cell proliferation, mytomycin C-treated DC were cultured with allogeneic T cells from a control.


RESULTS
When the T cell-stimulatory activity of DC was expressed as stimulation index value of [3H]-thymidine incorporation of T cells, the values were lower in HCV-infected HCC (2.6 +/- 1.8, P < 0.01) than in controls (5.5 +/- 2.0) and CH (5.0 +/- 1.3). Staphylococcus aureus Cowan 1-induced IL-12 production of DC was decreased in HCV-infected HCC (P < 0.001, P < 0.01 and P < 0.05, respectively) compared with controls, CH and LC, while similar amounts of IL-10 were produced in patients and controls. Interleukin-10 and IFN-gamma production of T cells in response to anti-CD3 antibody or IL-12 were equivalent between patient groups and controls, respectively. Similarly decreased DC function and normal T cell response were observed in HBV-infected HCC patients.


CONCLUSIONS
These findings suggest that the depressed function of DC is associated with pathogenesis of HCC with HBV or HCV infection.
Kakumu
S
S
First Department of Internal Medicine and Research Center for Infectious Disease, Aichi Medical University, Aichi-gun, Aichi-ken, Japan.
Ito
S
S
Ishikawa
T
T
Mita
Y
Y
Tagaya
T
T
Fukuzawa
Y
Y
Yoshioka
K
K
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006509:Hepatitis B / Q000150:complications / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology; D008113:Liver Neoplasms / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D016685:Mitomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor