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- Title
Expansion of circulating CD56<sup>bright</sup> natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α.
- Authors
Riley, Caroline H.; Hansen, Morten; Brimnes, Marie K.; Hasselbalch, Hans C.; Bjerrum, Ole W.; Straten, Per thor; Svane, Inge Marie; Jensen, Morten Krogh
- Abstract
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.
- Subjects
NEURAL cell adhesion molecule; MYELOPROLIFERATIVE neoplasms; INTERFERONS; KILLER cells; TUMOR immunology; IMMUNE response; CELLULAR recognition; THERAPEUTICS
- Publication
European Journal of Haematology, 2015, Vol 94, Issue 3, p227
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/ejh.12420