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-gamma, TNF-alpha) 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-gamma 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.

Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment / Maggio, Roberta; Peragine, Nadia; M. S., De Propris; Antonella, Vitale; Loredana, Elia; Elisabetta, Calabrese; DELLA STARZA, Irene; Stefania, Intoppa; Maria Laura, Milani; Guarini, Anna; Foa, Roberto. - In: CANCER IMMUNOLOGY, IMMUNOTHERAPY. - ISSN 0340-7004. - ELETTRONICO. - 60:4(2011), pp. 599-607. [10.1007/s00262-010-0966-2]

Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment

MAGGIO, ROBERTA;PERAGINE, NADIA;DELLA STARZA, IRENE;GUARINI, Anna;FOA, Roberto
2011

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-gamma, TNF-alpha) 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-gamma 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.
2011
dendritic cells; imatinib; ph + acute lymphoblastic leukemia (all) patients; ph+ acute lymphoblastic leukemia (all) patients; t cells
01 Pubblicazione su rivista::01a Articolo in rivista
Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment / Maggio, Roberta; Peragine, Nadia; M. S., De Propris; Antonella, Vitale; Loredana, Elia; Elisabetta, Calabrese; DELLA STARZA, Irene; Stefania, Intoppa; Maria Laura, Milani; Guarini, Anna; Foa, Roberto. - In: CANCER IMMUNOLOGY, IMMUNOTHERAPY. - ISSN 0340-7004. - ELETTRONICO. - 60:4(2011), pp. 599-607. [10.1007/s00262-010-0966-2]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/380101
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