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

• Published in: British journal of cancer Vol. 102; no. 4; pp. 748 - 753
• Main Authors: Behboudi, S, Alisa, A, Boswell, S, Anastassiou, J, Pathan, A A, Williams, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.02.2010; Nature Publishing Group
• Subjects: 631/67/580; 692/699/67/1504/1610; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins - immunology; Antigens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Case-Control Studies; Cytokines; Drug Resistance; Enzymes; Epidemiology; Female; Follow-Up Studies; Hepatitis C - complications; Hepatitis C - immunology; Humans; Immunoassay; Liver cancer; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - immunology; Liver Neoplasms - blood; Liver Neoplasms - complications; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Lymphocyte Activation - physiology; Lymphocytes; Male; Medical research; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neoplasm Staging; Oncology; Peptides; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; Th1 Cells - immunology; Th1 Cells - pathology; Tumors; Up-Regulation - immunology; United Kingdom > UK; United States > US; IFN; Child–Pugh; stage of disease; HCC; AFP; producing cells; Okuda
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605526

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.