Immunomodulatory Effects of STI571 in Chronic Myeloid Leukaemia.

Background: The tyrosine kinase inhibitor imatinib (imatinib, STI571, Glivec, and Gleevec) is highly effective in the treatment of chronic myeloid leukaemia (CML) and has already been shown to be effective in the setting of allogeneic stem cell transplantation. But until now, less is known with respect to its immunomodulating effects. Objective: In the present survey we investigated, whether imatinib could modify the antigen-presenting capacity of myeloid cells and in turn affects the cellular immune response. Method: For this purpose, patient derived chronic myeloid cells were incubated with different concentrations of imatinib (0, 1, 2, or 5microM), characterized for their antigen-presenting profile and their stimulatory capacity in the context of HLA-matched and mismatched T-cells. After 5 days, the proliferative immune response was evaluated in presence or absence of different concentrations of imatinib and altered effector-to-target ratios. Thereby, proliferation was detected via a CFDA, SE (5,6-carboxyfluorescein diacetate succinimidyl ester) based assay. Result: The proliferative capacity of the T- cells (allogeneic, HLA-mismatched) was inhibited by imatinib in a dose-dependent manner. Also, the expression of the activation markers was reduced in the presence of the different STI571 concentrations. Moreover, myeloid blasts were sensitized for T cell mediated effector functions by pre-treatment with increasing concentrations of imatinib. Conclusion: Taken together, imatinib can interfere with the T cellular immune response in vitro, and its impact on graft-versus-leukemia (GvL) and graft-versus-host (GvH) reactions will be further investigated.