Imatinib impairs CD8+ T lymphocytes specifically directed against the leukemia-associated antigen RHAMM/CD168 in vitro |
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Authors: | Jinfei Chen Anita Schmitt Baoan Chen Markus Rojewski Mark Ringhoffer Stephanie von Harsdorf Jochen Greiner Philippe Guillaume Hartmut Döhner Donald Bunjes Michael Schmitt |
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Institution: | (1) Third Department of Internal Medicine, University Ulm, Robert-Koch-Str 8, 89081 Ulm, Germany;(2) Key Laboratory of Development Genes and Human Diseases, Ministry of Education, Southeast University Medical School, Nanjing, 210009, China;(3) Department of Otorhinolaryngology, University Clinic, Ulm, Germany;(4) Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany;(5) Lausanne Branch of the Ludwig Institute for Cancer Research (LICR), Epalinges, Switzerland |
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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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Keywords: | Imatinib Lymphocyte proliferation Receptor for hyaluronic acid mediated motility Chronic myelogenous leukemia |
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