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Imatinib impairs CD8+ T lymphocytes specifically directed against the leukemia-associated antigen RHAMM/CD168 in vitro

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Abstract

The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate is highly effective in the front-line treatment of chronic myeloid leukemia (CML) and is increasingly used in patients with residual disease or relapse after allogeneic stem cell transplantation (allo-SCT). Since an impairment of anti-viral CD8+ T-lymphocyte function by imatinib has been described, we question whether imatinib also affects specific anti-leukemic CD8+ T lymphocytes generated from the peripheral blood of healthy donors, and of CML patients after allo-SCT. Here, we assessed CD8+ T-cell expansion and function from healthy donors and patients with CML. The release of IFN-γ and granzyme B by CD8+ T-lymphocytes specific for R3, a recently described T-cell epitope peptide derived from a leukemia-associated antigen designated RHAMM/CD168 (receptor for hyaluronic acid mediated motility), was inhibited by imatinib in a dose-dependent fashion (range: 1–25 μM). These T cells were able to lyse cognate peptide labeled T2 cells and CD34+ CML progenitor cells. This lysis was inhibited by imatinib. The inhibitory effect was not associated with an increased rate of apoptosis of T cells and reversible after removal of imatinib. In the light of these findings, clinical administration of imatinib might result in the reduction of efficacy of the graft-versus-leukemia effect or other T-cell-based immunotherapies.

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Acknowledgment

We thank Ms Goetz for her excellent technical support in this project. This research was kindly supported by Novartis, Nuremberg, Germany.

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Authors and Affiliations

  1. Third Department of Internal Medicine, University Ulm, Robert-Koch-Str 8, 89081, Ulm, Germany

    Jinfei Chen, Mark Ringhoffer, Stephanie von Harsdorf, Jochen Greiner, Hartmut Döhner, Donald Bunjes & Michael Schmitt

  2. Key Laboratory of Development Genes and Human Diseases, Ministry of Education, Southeast University Medical School, Nanjing, 210009, China

    Jinfei Chen & Baoan Chen

  3. Department of Otorhinolaryngology, University Clinic, Ulm, Germany

    Anita Schmitt

  4. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany

    Markus Rojewski

  5. Lausanne Branch of the Ludwig Institute for Cancer Research (LICR), Epalinges, Switzerland

    Philippe Guillaume

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  1. Jinfei Chen
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Correspondence to Michael Schmitt.

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Chen, J., Schmitt, A., Chen, B. et al. Imatinib impairs CD8+ T lymphocytes specifically directed against the leukemia-associated antigen RHAMM/CD168 in vitro. Cancer Immunol Immunother 56, 849–861 (2007). https://doi.org/10.1007/s00262-006-0232-9

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  • DOI: https://doi.org/10.1007/s00262-006-0232-9

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