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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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HCC patients with anti-AFP CD4 T-cells responses have significantly lower levels of serum AFP. Serum AFP levels in HCC patients with or without (A) anti-AFP total T-cells responses (both CD4 and CD8), (B) CD4 T-cell responses or (C) CD8 T-cell responses are shown. Anti-AFP CD4 T-cell response was detected in patients with low or moderately elevated serum AFP (n=0.018). Median of serum AFP levels for responders and non-responders are presented and each dot represents a patient with HCC.
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fig3: HCC patients with anti-AFP CD4 T-cells responses have significantly lower levels of serum AFP. Serum AFP levels in HCC patients with or without (A) anti-AFP total T-cells responses (both CD4 and CD8), (B) CD4 T-cell responses or (C) CD8 T-cell responses are shown. Anti-AFP CD4 T-cell response was detected in patients with low or moderately elevated serum AFP (n=0.018). Median of serum AFP levels for responders and non-responders are presented and each dot represents a patient with HCC.

Mentions: An AFP-specific CD4 T-cell response was mainly detected in HCC patients with normal or mildly elevated serum AFP (P=0.0188, Mann–Whitney U-test). In contrast, there was no significant difference in AFP concentrations between CD8 T-cell responders and non-responders (Figure 3A–C). Median serum AFP concentrations were 7.5-fold higher in HCC patients who lacked a CD4 T-cell response (non-responders) than in those who had a CD4 T-cell response (responders) (Figure 3B). There was also a significant difference in the number of patients with Okuda tumour stage I vs those with stage II or III in CD4 T-cell responders (χ2, P=0.04; 95% confidence intervals), whereas there was no difference in the number of patients with Okuda tumour stage I vs stage II or III in CD8 or total T-cell responders. This indicates that patients in stage II or III are significantly less likely to have an anti-AFP Th1 response, whereas anti-AFP Tc1 responses remain unchanged.


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)

HCC patients with anti-AFP CD4 T-cells responses have significantly lower levels of serum AFP. Serum AFP levels in HCC patients with or without (A) anti-AFP total T-cells responses (both CD4 and CD8), (B) CD4 T-cell responses or (C) CD8 T-cell responses are shown. Anti-AFP CD4 T-cell response was detected in patients with low or moderately elevated serum AFP (n=0.018). Median of serum AFP levels for responders and non-responders are presented and each dot represents a patient with HCC.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: HCC patients with anti-AFP CD4 T-cells responses have significantly lower levels of serum AFP. Serum AFP levels in HCC patients with or without (A) anti-AFP total T-cells responses (both CD4 and CD8), (B) CD4 T-cell responses or (C) CD8 T-cell responses are shown. Anti-AFP CD4 T-cell response was detected in patients with low or moderately elevated serum AFP (n=0.018). Median of serum AFP levels for responders and non-responders are presented and each dot represents a patient with HCC.
Mentions: An AFP-specific CD4 T-cell response was mainly detected in HCC patients with normal or mildly elevated serum AFP (P=0.0188, Mann–Whitney U-test). In contrast, there was no significant difference in AFP concentrations between CD8 T-cell responders and non-responders (Figure 3A–C). Median serum AFP concentrations were 7.5-fold higher in HCC patients who lacked a CD4 T-cell response (non-responders) than in those who had a CD4 T-cell response (responders) (Figure 3B). There was also a significant difference in the number of patients with Okuda tumour stage I vs those with stage II or III in CD4 T-cell responders (χ2, P=0.04; 95% confidence intervals), whereas there was no difference in the number of patients with Okuda tumour stage I vs stage II or III in CD8 or total T-cell responders. This indicates that patients in stage II or III are significantly less likely to have an anti-AFP Th1 response, whereas anti-AFP Tc1 responses remain unchanged.

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