{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:24:12Z","timestamp":1792718652299,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T00:00:00Z","timestamp":1265587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In chronic myeloid leukemia (CML), BCR\/ABL\u2010mediated oncogenic signaling can be targeted with the BCR\/ABL\u2010inhibitors Imatinib, Nilotinib and Dasatinib. However, these agents may also affect anti\u2010tumor immunity. Here, we analyzed the effects of the 3 BCR\/ABL\u2010inhibitors on natural killer (NK) cell reactivity. Exposure of CML cells (K562, Meg\u201001) to pharmacological concentrations of Imatinib, Nilotinib and Dasatinib diminished expression of ligands for the activating immunoreceptor NKG2D to a similar extent. This resulted in comparably reduced NK cell cytotoxicity and IFN\u2010\u03b3 production. When direct effects on NK cell responses to K562 and primary CML cells as well as activating cytokines were studied, Dasatinib was found to abrogate NK cytotoxicity and cytokine production. Nilotinib did not alter cytotoxicity but, at high levels, impaired NK cytokine production, while Imatinib had no direct influence on NK cell reactivity. Of note, Nilotinib, but not the other BCR\/ABL\u2010inhibitors increased cell death within the preferentially cytokine\u2010secreting CD56<jats:sup>bright<\/jats:sup>CD16<jats:sup>\u2212<\/jats:sup> NK cell subset, which may, at least in part, serve to explain the effect of Nilotinib on NK cytokine production. Analysis of NK cell signaling revealed that Dasatinib inhibited proximal signaling events leading to decreased phosphorylation of PI3K and ERK that are crucial for NK cell reactivity. Imatinib and Nilotinib, in contrast, showed no relevant effect on NK cell PI3K or ERK activity. In light of the potential role of NK cells in the immunesurveillance of residual leukemia and for future combinatory immunotherapeutic approaches, our data indicate that choice and dosing of the most suitable BCR\/ABL\u2010inhibitor for a given patient require careful consideration.<\/jats:p>","DOI":"10.1002\/ijc.25233","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T18:30:08Z","timestamp":1265653808000},"page":"2119-2128","source":"Crossref","is-referenced-by-count":78,"title":["The BCR\/ABL\u2010inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity"],"prefix":"10.1002","volume":"127","author":[{"given":"Julia","family":"Salih","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hilpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Placke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Gr\u00fcnebach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Steinle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut 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