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Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease.

Behboudi S, Alisa A, Boswell S, Anastassiou J, Pathan AA, Williams R - Br. J. Cancer (2010)

Bottom Line: alpha-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy.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.Therefore, these data provide valuable information for the design of vaccination strategies against HCC.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hepatology, University College London, UK. s.behboudi@ucl.ac.uk

ABSTRACT

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.

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.

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Multi-specific CD4 and CD8 T-cell responses in HCC patients and controls. Expanded T cells were incubated with indicated AFP peptides and peptide-specific intracellular IFNγ was analysed using flow cytometry. Naturally occurring CD4 and CD8 T-cell responses against individual AFP-derived peptides were analysed in three patients with HCC and in three controls. The percentages of peptide-specific CD4 (black) or CD8 (grey) T-cell responses to individual peptides are shown.
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fig2: Multi-specific CD4 and CD8 T-cell responses in HCC patients and controls. Expanded T cells were incubated with indicated AFP peptides and peptide-specific intracellular IFNγ was analysed using flow cytometry. Naturally occurring CD4 and CD8 T-cell responses against individual AFP-derived peptides were analysed in three patients with HCC and in three controls. The percentages of peptide-specific CD4 (black) or CD8 (grey) T-cell responses to individual peptides are shown.

Mentions: To determine the reacting peptide(s) within the peptide pools, expanded T cells were treated with individual peptides of the reacting pools, and peptide-specific intracellular IFN-γ production by CD4 and CD8 T cells was analysed using flow cytometry (Figure 2). Among the responders, PBMCs were available from LC01, LC03, NC02, HCC06, HCC20 and HCC25 for further studies. Dot plots of anti-AFP-specific IFN-γ-producing CD4 or CD8 T cells from these individuals are shown (Supplementary Figures 1 and 2). These results suggest that Th1 and Tc1 responses are multi-specific.


Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease.

Behboudi S, Alisa A, Boswell S, Anastassiou J, Pathan AA, Williams R - Br. J. Cancer (2010)

Multi-specific CD4 and CD8 T-cell responses in HCC patients and controls. Expanded T cells were incubated with indicated AFP peptides and peptide-specific intracellular IFNγ was analysed using flow cytometry. Naturally occurring CD4 and CD8 T-cell responses against individual AFP-derived peptides were analysed in three patients with HCC and in three controls. The percentages of peptide-specific CD4 (black) or CD8 (grey) T-cell responses to individual peptides are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837570&req=5

fig2: Multi-specific CD4 and CD8 T-cell responses in HCC patients and controls. Expanded T cells were incubated with indicated AFP peptides and peptide-specific intracellular IFNγ was analysed using flow cytometry. Naturally occurring CD4 and CD8 T-cell responses against individual AFP-derived peptides were analysed in three patients with HCC and in three controls. The percentages of peptide-specific CD4 (black) or CD8 (grey) T-cell responses to individual peptides are shown.
Mentions: To determine the reacting peptide(s) within the peptide pools, expanded T cells were treated with individual peptides of the reacting pools, and peptide-specific intracellular IFN-γ production by CD4 and CD8 T cells was analysed using flow cytometry (Figure 2). Among the responders, PBMCs were available from LC01, LC03, NC02, HCC06, HCC20 and HCC25 for further studies. Dot plots of anti-AFP-specific IFN-γ-producing CD4 or CD8 T cells from these individuals are shown (Supplementary Figures 1 and 2). These results suggest that Th1 and Tc1 responses are multi-specific.

Bottom Line: alpha-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy.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.Therefore, these data provide valuable information for the design of vaccination strategies against HCC.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hepatology, University College London, UK. s.behboudi@ucl.ac.uk

ABSTRACT

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.

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.

Show MeSH
Related in: MedlinePlus