Decreased functional T lymphocyte-mediated cytokine responses in patients with chemotherapy-induced neutropenia

Authors

  • L. Öhrmalm,

    Corresponding author
    1. Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
    • Correspondence: Lars Öhrmalm, Center for Molecular Medicine, Infectious Diseases Unit, L8:01, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.

      (fax: +46-8 51776182; e-mail: lars.ohrmalm@ki.se).

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  • C. Smedman,

    1. Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    2. Mabtech AB, Nacka Strand, Sweden
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  • M. Wong,

    1. Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • K. Broliden,

    1. Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • T. Tolfvenstam,

    1. Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • O. Norbeck

    1. Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Abstract

Objectives

The degree of immunosuppression in patients with haematological malignancies treated with chemotherapy is routinely measured as number of circulating cells (preferable neutrophils) in peripheral blood. A parallel decline in the number of T cells is expected, but a possible alteration in their functionality has been less well explored. The ability of T cells to secrete more than one cytokine simultaneously is known to indicate protective immunity. The aim of this study was to determine whether the function of circulating T cells is altered in patients with chemotherapy-induced neutropenia.

Design, setting and subjects

In this cross-sectional study, we used the FluoroSpot assay to investigate the proportion of T cells secreting either interferon-γ or interleukin-2, or both cytokines simultaneously, after anti-CD3 stimulation. Peripheral blood mononuclear cells from 53 adult patients with chemotherapy-induced neutropenia and 20 healthy individuals were investigated.

Results

There were significantly fewer T cells secreting interferon-γ in patients with neutropenia compared with healthy control subjects (= 0.02), but the difference was greatest for dual cytokine-secreting T cells (= 0.001). Furthermore, the amount of secreted cytokine per T cell appeared to be reduced in patients, compared with control subjects.

Conclusion

Our results suggest that the functionality of T cells is altered in patients with haematological malignancies with chemotherapy-induced neutropenia. In parallel with a decline in T cell count, this may further increase the risk of severe infections.

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