Cancer Immunology, Immunotherapy

, Volume 56, Issue 6, pp 913–925 | Cite as

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

  • Elisabeth Ersvær
  • Peter Hampson
  • Kimberley Hatfield
  • Elling Ulvestad
  • Øystein Wendelbo
  • Janet M. Lord
  • Bjørn Tore Gjertsen
  • Øystein Bruserud
Original Article

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

Cytopenia T lymphocytes Chemotherapy Cytokines 

Notes

Acknowledgments

The work was supported by the Norwegian Cancer Society and the European commission (LSHB-CT-2004–503467). The technical assistance of Kristin Paulsen and Aina Kvinnsland is gratefully acknowledged.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Elisabeth Ersvær
    • 1
  • Peter Hampson
    • 3
  • Kimberley Hatfield
    • 1
  • Elling Ulvestad
    • 4
  • Øystein Wendelbo
    • 1
    • 2
  • Janet M. Lord
    • 3
  • Bjørn Tore Gjertsen
    • 1
  • Øystein Bruserud
    • 1
  1. 1.Section for Hematology, Institute of MedicineThe University of Bergen and Haukeland University HospitalBergenNorway
  2. 2.Division for Infectious DiseasesThe University of Bergen and Haukeland University HospitalBergenNorway
  3. 3.MRC Centre for Immune RegulationThe University of BirminghamBirminghamUK
  4. 4.Department of Microbiology and Immunology and The Gade InstituteHaukeland University Hospital and The University of BergenBergenNorway

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