尼罗替尼和干扰素-α治疗慢性髓性白血病患者的免疫调节

The addition of interferon to tyrosine kinase inhibitors (TKIs), to improve deep molecular response (DMR) and potentially treatment-free remission (TFR) rates in chronic-phase chronic myeloid leukaemia (CP-CML) patients is under active investigation.

However, the immunobiology of this combination is poorly understood.

We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon-alpha (IFN- ) within the ALLG CML11 trial (n = 12) or nilotinib alone (n = 17).

We demonstrate that nilotinib+IFN transiently reduced absolute counts of natural killer (NK) cells, compared with nilotinib alone.

Furthermore, CD16 + -cytolytic and CD57 + CD62L - -mature NK cells were transiently reduced during IFN therapy, without affecting NK-cell function. IFN transiently increased cytotoxic T-lymphocyte (CTL) responses to leukaemia-associated antigens (LAAs) proteinase-3, BMI-1 and PRAME; and had no effect on regulatory T cells, or myeloid-derived suppressor cells. Patients on nilotinib+IFN who achieved MR4.

5 by 12 months had a significantly higher proportion of NK cells expressing NKp46, NKp30 and NKG2D compared with patients not achieving this milestone. This difference was not observed in the nilotinib-alone group. The addition of IFN to nilotinib drives an increase in NK-activating receptors, CTLs responding to LAAs and results in transient immune modulation, which may influence earlier DMR, and its effect on long-term outcomes warrants further investigation.