IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia

Immune modulation in chronic myeloid leukaemia patients treated with nilotinib and interferon‐alpha

“…Although IFN is generally believed to activate NK cells, 42 we observed a general downregulation of activation and cytotoxicity receptors, including CD16, CD57, NCRs, NKG2D and upregulation of the inhibitory CD62L receptor compared with nilotinib alone. Interestingly, these changes did not alter NK‐cell function, with a non‐significant increase in NK‐cell degranulation after addition of IFN compared with diagnosis, which was in keeping with a recent report by Huuhtanen et al 39 We speculate that prolonged IFN therapy and reducing leukaemic load may lead to downregulation of activating receptors on NK cells as the immune milieu reverts from a pro‐inflammatory to a more normalised state 26 . We assessed whether the observed immunological changes were associated with achievement of MR4.5 at 12 months.…”

“…We also found that CM T cells were reduced in the CML11 cohort compared with nilotinib monotherapy and that there was a concomitant increase in TDEM cells, driven mainly by increased CD4 + ‐TDEM numbers at both IFN timepoints. In contrast, a recent report assessing immunological changes with dasatinib+IFN found an increase in CM‐CD4 + and CD8 + T cells with IFN addition, and a concomitant decrease in CD8 + TEMRA cells 39 . These differences may be due to the distinct properties of dasatinib, which is associated with more immune phenomena than nilotinib 43,44 .…”

“…We observed a significant decrease in absolute NK cells in patients treated with IFN at the late timepoint, which was reversed 4 months after IFN discontinuation. Reduced NK cells were also found when IFN was combined with dasatinib 39 and when nilotinib+IFN was administered to patients who failed to reach DMR on imatinib 40 . Kreutzman et al also found that patients on IFN therapy had lower absolute NK cells than those who had ceased IFN, albeit in TKI‐naïve patients 41 .…”

“…In contrast, a recent report assessing immunological changes with dasatinib+IFN found an increase in CM-CD4 and CD8 + T cells with IFN addition, and a concomitant decrease in CD8 + TEMRA cells. 39 These differences may be due to the distinct properties of dasatinib, which is associated with more immune phenomena than nilotinib. 43,44 Type I interferons generally activate T cells, including CD4 + T cells, and drive T cells to a CM phenotype.…”

“…22 We speculate this may be due to improved immune surveillance in the context of minimal residual disease, although there may be other immunological signatures which we have not captured, such as widening of the immune repertoire and alterations to immune cell interactions. 39 We sought to delineate the possible immune mechanisms which may be responsible for the observed higher rates of DMR seen in CP-CML patients who receive nilotinib+IFN.…”