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Immunocompetent cell functions in Ph(+) acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment.
MedLine Citation:
PMID:  21240485     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-15
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  -     ISSN:  1432-0851     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Via Benevento 6, 00161, Rome, Italy.
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