Cancer Immunology, Immunotherapy

, Volume 56, Issue 12, pp 1931–1943

Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with AFP-positive hepatocellular cancer

Authors

    • Department of Medicine, Surgery and Immunology University of Pittsburgh Cancer InstituteUniversity of Pittsburgh
    • Hillman Cancer Center, Research PavilionUniversity of Pittsburgh
  • Antoni Ribas
    • Divisions of Surgical OncologyUniversity of California
    • Hematology/OncologyUniversity of California
  • Douglas M. Potter
    • UPCI BiostatisticsUniversity of Pittsburgh
  • James S. Economou
    • Divisions of Surgical OncologyUniversity of California
    • Department of Microbiology, Immunology and Molecular GeneticsUniversity of California
Original Article

DOI: 10.1007/s00262-007-0337-9

Cite this article as:
Butterfield, L.H., Ribas, A., Potter, D.M. et al. Cancer Immunol Immunother (2007) 56: 1931. doi:10.1007/s00262-007-0337-9

Abstract

We are investigating the use of Alpha Fetoprotein (AFP) as a tumor rejection antigen for hepatocellular carcinoma (HCC). We recently completed vaccination of 10 AFP+/HLA-A2.1+ HCC subjects with AFP peptide-pulsed autologous dendritic cells (DC). There were increased frequencies of circulating AFP-specific T cells and of IFNγ-producing AFP-specific T cells after vaccination. In order to better understand the lack of association between immune response and clinical response, we have examined additional aspects of the AFP immune response in patients. Here, we have characterized the cell surface phenotype of circulating AFP tetramer-positive CD8 T cells and assessed AFP-specific CD4 function. Before vaccination, HCC subjects had increased frequencies of circulating AFP-specific CD8 T cells with a range of naïve, effector, central and effector memory phenotypes. Several patients had up-regulated activation markers. A subset of patients was assessed for phenotypic changes pre- and post-vaccination, and evidence for complete differentiation to effector or memory phenotype was lacking. CD8 phenotypic and cytokine responses did not correlate with level of patient serum AFP antigen (between 74 and 463,040 ng/ml). Assessment of CD4+ T cell responses by ELISPOT and multi-cytokine assay did not identify any spontaneous CD4 T cell responses to this secreted protein. These data indicate that there is an expanded pool of partially differentiated AFP-specific CD8 T cells in many of these HCC subjects, but that these cells are largely non-functional, and that a detectable CD4 T cell response to this secreted oncofetal antigen is lacking.

Keywords

Alpha fetoproteinImmunotherapyT lymphocytesImmunological monitoringCancer vaccine

Abbreviations

AFP

Alpha fetoprotein

AFP+

AFP-expressing

HCC

Hepatocellular cancer

DC

Dendritic cell(s)

PBMC

Peripheral blood mononuclear cells

Copyright information

© Springer-Verlag 2007