Cancer Immunology, Immunotherapy

, Volume 56, Issue 6, pp 913–925

T cells remaining after intensive chemotherapy for acute myelogenous leukemia show a broad cytokine release profile including high levels of interferon-γ that can be further increased by a novel protein kinase C agonist PEP005

Authors

    • Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University Hospital
  • Peter Hampson
    • MRC Centre for Immune RegulationThe University of Birmingham
  • Kimberley Hatfield
    • Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University Hospital
  • Elling Ulvestad
    • Department of Microbiology and Immunology and The Gade InstituteHaukeland University Hospital and The University of Bergen
  • Øystein Wendelbo
    • Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University Hospital
    • Division for Infectious DiseasesThe University of Bergen and Haukeland University Hospital
  • Janet M. Lord
    • MRC Centre for Immune RegulationThe University of Birmingham
  • Bjørn Tore Gjertsen
    • Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University Hospital
  • Øystein Bruserud
    • Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University Hospital
Original Article

DOI: 10.1007/s00262-006-0236-5

Cite this article as:
Ersvær, E., Hampson, P., Hatfield, K. et al. Cancer Immunol Immunother (2007) 56: 913. doi:10.1007/s00262-006-0236-5

Abstract

Cytokines are released during T cell activation, including the potentially anti-leukemic interferon-γ (IFNγ), but also the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) that enhance proliferation and inhibit apoptosis of acute myelogenous leukemia (AML) cells. In the present study we investigated the release of IFNγ and GM-CSF by circulating T cells in AML patients with chemotherapy-induced cytopenia. T cells were activated with anti-CD3 plus anti-CD28 in a whole-blood assay in the presence of their natural cytokine network. We examined 63 samples derived from 16 AML patients during 28 chemotherapy cycles. Activated T cells showed a broad cytokine release profile, but IFNγ and GM-CSF levels showed a significant correlation and were generally higher than the other cytokine levels. Higher IFNγ and GM-CSF responses were associated with a low CD4:CD8 ratio, older patient age and no ongoing chemotherapy indicating potential utility of T cell activation regimes for the older AML patient. The cytokine levels could be further increased by the novel protein kinase C agonist PEP005, which also induced significant production of IL2 and TNFα which could contribute to anti-tumor effects in AML patients. We conclude that remaining T cells after intensive AML therapy show a broad cytokine release profile including high and significantly correlated levels of potentially anti-leukemic IFNγ and the AML growth factor GM-CSF. The final outcome of an AML-initiated T cell cytokine response will thus depend on the functional characteristics of the AML cells, in particular the relative expression of IFNγ and GM-CSF receptors which differs between AML patients.

Keywords

CytopeniaT lymphocytesChemotherapyCytokines

Copyright information

© Springer-Verlag 2006