Immunological off-target effects of imatinib

Imatinib does not affect Philadelphia-chromosome-positive haematopoietic stem cells in patients achieving molecular response (MR); however, prolonged relapse-free survival can be achieved before treatment discontinuation, implying that efficient immunosurveillance has been establishedIn addition to targeting tumoural BCR–ABL1 and KIT oncogene products, imatinib modulates protein tyrosine kinases involved in key signalling pathways in both effector and regulatory immune cells implicated in cancer immunosurveillanceLow-dose imatinib has stimulatory effects on haematopoiesis and can contribute to immune-mediated clearance of pathogensIn patients with chronic myeloid leukaemia, imatinib elicits antigen-specific T-cell responses that can protect against relapses in patients with cytogenetically controlled or minimal diseaseImatinib boosts natural killer-cell-induced IFNα secretion and decreases regulatory T-cell numbers in patients with gastrointestinal tumours; NKp30 isoform patterns dictate the prognosis of the diseaseWe propose that novel treatment regimens combining imatinib with immunotherapies will enable long-term relapse-free survival to be achieved in a larger number of patients and will prevent the emergence of imatinib-resistant clones