Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease.
BACKGROUND
alpha-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients.


METHODS
We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-gamma.


RESULTS
Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child-Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child-Pugh A score and in 46% with a B or C score.


CONCLUSIONS
These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.
Behboudi
S
S
Institute of Hepatology, University College London, UK. s.behboudi@ucl.ac.uk
Alisa
A
A
Boswell
S
S
Anastassiou
J
J
Pathan
A A
AA
Williams
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000150:complications / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology; D000509:alpha-Fetoproteins / Q000276:immunology*
D000509:alpha-Fetoproteins