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- Title
Immunocompetent cell functions in Ph acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment.
- Authors
Maggio, Roberta; Peragine, Nadia; Propris, Maria; Vitale, Antonella; Elia, Loredana; Calabrese, Elisabetta; Della Starza, Irene; Intoppa, Stefania; Milani, Maria; Guarini, Anna; Foà, Robin
- 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.
- Subjects
LYMPHOBLASTIC leukemia treatment; IMATINIB; PROTEIN-tyrosine kinase inhibitors; IMMUNOCOMPETENT cells; T cells; IMMUNOREGULATION; INTERFERONS; KILLER cells
- Publication
Cancer Immunology, Immunotherapy, 2011, Vol 60, Issue 4, p599
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-010-0966-2