title: Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α.
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 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.
authors.affiliation: Department of Haematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Riley
authors.forename: Morten
authors.initials: M
authors.lastname: Hansen
authors.forename: Marie K
authors.initials: MK
authors.lastname: Brimnes
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hasselbalch
authors.forename: Ole W
authors.initials: OW
authors.lastname: Bjerrum
authors.forename: Per Thor
authors.initials: PT
authors.lastname: Straten
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.forename: Morten Krogh
authors.initials: MK
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology; D053614:Janus Kinase 2 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D019002:CD56 Antigen; C569274:IL15 protein, human; D007155:Immunologic Factors; D016898:Interferon-alpha; D019409:Interleukin-15; C522918:NCAM1 protein, human; D018664:Interleukin-12; D007371:Interferon-gamma; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea
keywords: IFN-α treatment; JAK2-positive MPNs; NK cells