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Title: | Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease |
Authors: | Alisa, A Boswell, S Anastassiou, J Pathan, AA Williams, R |
Keywords: | AFP;HCC;Stage of disease;Okuda;Child-Pugh;IFN-gamma-producing cells |
Issue Date: | 2010 |
Publisher: | Nature Publishing Group |
Citation: | British Journal of Cancer, 102, 748 - 753, 2010 |
Abstract: | Background: α-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-γ. 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. Conclusion: 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. |
Description: | Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
URI: | http://www.nature.com/bjc/journal/v102/n4/full/6605526a.html http://bura.brunel.ac.uk/handle/2438/8422 |
DOI: | http://dx.doi.org/10.1038/sj.bjc.6605526 |
ISSN: | 0007-0920 |
Appears in Collections: | Biological Sciences Publications Dept of Life Sciences Research Papers |
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