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‐α. IFN‐α 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‐α 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‐α 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‐γ expression by CD56^dim NK cells during IFN‐α treatment was observed. In contrast, our data indicate a compromised NK cell response to target‐cell recognition during treatment with IFN‐α 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‐α, P = 0.02. Based on our findings, one might speculate whether treatment with IFN‐α 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.