Z Gastroenterol 2010; 48 - P4_50
DOI: 10.1055/s-0029-1246542

AFP-specific CD4+ T-cell immunity in the blood and liver of patients with Hepatocellular Carcinoma

M Witkowski 1, N Semmo 1, R Thimme 1, N Kersting 1
  • 1Abteilung Innere Medizin II, Medizinische Universitätsklinik Freiburg, Freiburg

Background: Hepatocellular Carcinoma (HCC) is one of the most common malignancies with limited therapeutic options. Alpha-fetoprotein (AFP) is a tumor-associated antigen in HCC and is a target for the development of cancer vaccine. Until recently, most studies on HCC have analyzed AFP-specific CD8+ T-cell responses. However, less is known about AFP-specific CD4+ T-cell responses.

Aim: In this study we characterized the frequency and function of AFP-specific CD4+ T-cell responses in a cohort of patients with HCC in blood and liver.

Methods: Peripheral blood and intrahepatic lymphocytes of patients with HCC and healthy donors were stimulated ex vivo and in vitro with overlapping peptides spanning the entire AFP-protein. AFP-specific CD4+ T-cell responses were analyzed by intracellular Interferon-γ staining.

Results: Ex vivo no AFP-specific CD4+ T-cell responses were detectable in the blood. However, after in vitro stimulation AFP-specific T cell responses could be detected in 50% of all patients with HCC. These immune responses were targeting different previously unreported epitopes with no immunodominant epitope recognizable.

After unspecific expansion of peripheral blood and intrahepatic lymphocytes AFP-specific CD4+ T-cell responses could be detected in 22% of the patients in the intrahepatic compartment but were not detectable in the peripheral blood indicating an enrichment of AFP-specific CD4+ T cells in the liver.

In contrast, AFP-specific CD8+ T-cell responses were found with a frequency of 50% in both peripheral blood an in the intrahepatic compartment. These findings suggest a general lack of AFP-specific CD4+ T-cell responses in patients with HCC.

Conclusion: AFP-specific CD4+ T-cell responses are part of the CD4+ T-cell pool and could be expanded in vitro. But potent immune responses of helper T cells to this oncofetal antigen are lacking in the majority of patients with HCC. This lack may facilitate tumor cells to escape the immune control.