Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α

In recent years, major molecular remissions have been observed in patients with JAK2-positive chronic myeloproliferative neoplasms (MPNs) after therapy with IFN-. IFN- is known to have altering effects on immune cells involved in immune surveillance and might consequently enhance anti-tumor immune response against the JAK2-mutated clone. The objective of this study was to investigate circulating levels and phenotype of natural killer cells in 29 JAK2-positive MPN patients during IFN- treatment. Furthermore, functional studies of NK cells upon target-cell recognition and cytokine stimulation were performed. The CD56(bright) and CD56(dim) NK cell subtypes display different properties in terms of cytokine production and cytotoxicity, respectively. Our results show a significant increase in the proportion of CD56(bright) NK cells and a decreasing CD56(dim) population during treatment with IFN- compared to patients that are untreated, treated with hydroxyurea and healthy controls, P<0.0001. Furthermore, an overall increase in cytokine-dependent (IL-12 and IL-15) IFN- expression by CD56(dim) NK cells during IFN- treatment was observed. In contrast, our data indicate a compromised NK cell response to target-cell recognition during treatment with IFN- in four patients. We also report low levels of circulating NK cells in untreated patients compared to healthy donors, patients treated with hydroxyurea and IFN-, P=0.02. Based on our findings, one might speculate whether treatment with IFN- skews the human NK population toward a helper type that may assist in CD8(+) T cell priming in lymphoid tissues at the expense of their immediate cytotoxic functions in peripheral blood and tissues.