Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment.
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| Abstract |
Imatinib mesylate (Imatinib) is a potent inhibitor of defined tyrosine kinases and is effectively used for the treatment of malignancies characterized by the constitutive activation of these tyrosine kinases, such as Philadelphia chromosome-positive (Ph(+)) leukemias and gastrointestinal stromal tumors. Suppressive as well as stimulating effects of this drug on T lymphocytes or dendritic cells (DC), which play a major role in immune tumor surveillance, have been reported. For this reason, we questioned whether Imatinib could also affect the phenotypic and functional properties of these subpopulations in Ph(+) acute lymphoblastic leukemia (ALL) patients on prolonged Imatinib maintenance treatment. Circulating T lymphocytes and NK cells from Imatinib-treated Ph(+) ALL patients showed a subset distribution comparable to that of healthy donors. In addition, T-cell immunomodulant cytokine production (IFN-γ, TNF-α) and proliferative responses were not impaired. A normal monocyte-derived DC differentiation and apoptotic body loading capacity was also observed in the majority of Imatinib-treated patients. In contrast, an impairment in the DC intracellular production of IL-12 was recorded, although this was not observed when normal DC were exposed in vitro to Imatinib. Finally, in vivo Imatinib treatment did not affect the T-lymphocyte proliferation and IFN-γ production induced by leukemic apoptotic body-loaded DC, underling the potential capability of these cells to generate a specific immune response against tumoral antigens. Taken together, these findings provide evidence that immunotherapeutic approaches aimed at controlling residual disease in Ph(+) ALL patients in hematologic remission are not jeopardized by the long-term administration of Imatinib.
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| Authors | Roberta Maggio, Nadia Peragine, Maria Stefania De Propris, Antonella Vitale, Loredana Elia, Elisabetta Calabrese, Irene Della Starza, Stefania Intoppa, Maria Laura Milani, Anna Guarini, Robin Foà |
| Journal | Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 60 Issue 4 Pg. 599-607 (Apr 2011) ISSN: 1432-0851 [Electronic] Germany |
| PMID | 21240485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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