Enlarged Memory T-Cell Pool and Enhanced Th1-Type Responses in Chronic Myeloid Leukemia Patients Who Have Successfully Discontinued IFN-a Monotherapy

A small proportion of chronic myeloid leukemia patients treated with interferon-a (IFN-a) monotherapy are able to discontinue the treatment without disease relapse although residual leukemia cells are present. Recently, we showed that these patients have increased amount of NK-cells and a distinct blood cytokine profile. We now aimed to study the function of NK- and T-cells in order to understand the role of the immune system in maintaining the treatment response after IFN-a discontinuation. The study included 13 patients: 5 patients were still treated with IFN-a monotherapy (IFN-ON, median treatment time 163 months) and 8 had stopped the treatment successfully (IFN-OFF, median time without therapy 42 months). Detailed immunophenotype and cytokine production of NK- and T-cells was analyzed with flow cytometry. In addition, the cytotoxicity of NK-cells was studied using K562 as target cells and both the degranulation and direct killing was measured. Compared to healthy controls, IFN-OFF patients had increased proportion of CD4+ effector memory (CCR72CD45RA2; median 23 % vs. healthy 16%, p = 0.009) and CD8+ central memory T-cells (CCR7+CD45RA2; median 26% vs. healthy 14%, p = 0.004). Further, upon stimulation the IFN-c/TNF-a cytokine secretion by CD4+ T-cells was significantly enhanced in IFN-OFF patients (median 13.7 % vs. healthy 7.8%, p = 0.01), and CD4+ effector and central memory cells were the main cytokine producers. No similar increase was observed in IFN-ON group (6.5%). In addition, the proportion of NK-cells was significantly increased in IFN-OFF patients (median IFN-OFF 24%, healthy 13%, p = 0.04), but their direct killing o