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

Caroline H. Riley, Morten Hansen, Marie K. Brimnes, Hans C. Hasselbalch, Ole W. Bjerrum, Per thor Straten, Inge Marie Svane, Morten Krogh Jensen

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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 CD56bright and CD56dim NK cell subtypes display different properties in terms of cytokine production and cytotoxicity, respectively. Our results show a significant increase in the proportion of CD56bright NK cells and a decreasing CD56dim 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 CD56dim 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.

OriginalsprogEngelsk
Sider (fra-til)227-234
Antal sider8
TidsskriftEuropean Journal of Haematology
Vol/bind94
Udgave nummer3
DOI
StatusUdgivet - 1 mar. 2015

Fingeraftryk Udforsk hvilke forskningsemner 'Expansion of circulating CD56<sup>bright</sup> natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α' indeholder.

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