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

doi:10.1111/ejh.12420

Expansion of circulating CD56^bright 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

Institut for Klinisk Medicin

29 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Haematology
Vol/bind	94
Udgave nummer	3
Sider (fra-til)	227–234
Antal sider	8
ISSN	0902-4441
DOI	https://doi.org/10.1111/ejh.12420
Status	Udgivet - 1 mar. 2015

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1111/ejh.12420

Citationsformater

Riley, C. H., Hansen, M., Brimnes, M. K., Hasselbalch, H. C., Bjerrum, O. W., Straten, P. T., Svane, I. M., & Jensen, M. K. (2015). Expansion of circulating CD56^bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α. European Journal of Haematology, 94(3), 227–234. https://doi.org/10.1111/ejh.12420

Expansion of circulating CD56^bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α. / Riley, Caroline H; Hansen, Morten; Brimnes, Marie K et al.

I: European Journal of Haematology, Bind 94, Nr. 3, 01.03.2015, s. 227–234.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{1593d1e1bbaa43f898bae224a71f6a07,

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 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.",

author = "Riley, {Caroline H} and Morten Hansen and Brimnes, {Marie K} and Hasselbalch, {Hans C} and Bjerrum, {Ole W} and Straten, {Per Thor} and Svane, {Inge Marie} and Jensen, {Morten Krogh}",

note = "{\textcopyright} 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2015",

month = mar,

day = "1",

doi = "10.1111/ejh.12420",

language = "English",

volume = "94",

pages = "227–234",

journal = "European Journal of Haematology",

issn = "0902-4441",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α

AU - Riley, Caroline H

AU - Hansen, Morten

AU - Brimnes, Marie K

AU - Hasselbalch, Hans C

AU - Bjerrum, Ole W

AU - Straten, Per Thor

AU - Svane, Inge Marie

AU - Jensen, Morten Krogh

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

U2 - 10.1111/ejh.12420

DO - 10.1111/ejh.12420

M3 - Journal article

C2 - 25082025

SN - 0902-4441

VL - 94

SP - 227

EP - 234

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 3

ER -