Cirrhotic Patients With or Without Hepatocellular Carcinoma Harbour AFP-Specific T-Lymphocytes That Can Be Activated in vitro by Human Alpha-Fetoprotein

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Abstract
Alpha-fetoprotein (AFP) is re-expressed in 60%-70% of hepatocellular carcinomas (HCC) and may therefore be a potential target for a prophylactic or therapeutic tumour-specific vaccination. A prerequisite for this approach is the possibility to induce AFP-specific T-lymphocytes in patients with HCC and/or cirrhosis. Peripheral blood was examined for the presence of AFP-specific T-lymphocytes using a FACS-based interferon-gamma secretion assay. In a group of healthy volunteers, the presence of AFP-specific CD4- and CD8-lymphocytes was demonstrated. Screening of blood of 14 cirrhotic patients without HCC and 23 cirrhotic patients with HCC showed that patients with liver diseases that represent targets for vaccination also harbour CD4-positive as well as CD8-positive AFP-specific Tlymphocytes. AFP reactivity in patients' lymphocytes was not significantly influenced by soluble serum AFP. The median stimulation factors for CD4-positive T-lymphocytes were significantly higher (P = 0.0365) in cirrhotic patients without HCC (median 2.08, range 0.50-4.40) compared to cirrhotic patients with HCC (median 1.15, range 0.24-8.50). AFP-specific T-lymphocytes that may be instrumental in HCC vaccination strategies are present in humans. This study suggests that immunopreventive vaccination of cirrhotic patients rather than immunotherapeutic vaccination of HCC patients may be preferable.

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