Interferon‐α induces marked alterations in circulating regulatory T cells, NK cell subsets, and dendritic cells in patients with JAK2V617F‐positive essential thrombocythemia and polycythemia vera. (26th November 2015)

• Record Type: Journal Article
• Authors: Riley, Caroline H.; Brimnes, Marie K.; Hansen, Morten; Jensen, Morten Krogh; Hasselbalch, Hans C.; Kjaer, Lasse; Straten, Per thor; Svane, Inge Marie
• Is Part Of: European journal of haematology. Volume 97:Number 1(2016:Jul.)
• Page Start: 83
• Page End: 92
• Publication Date: 2015-11-26
• Subjects: IFN‐α treatment -- JAK2‐positive MPNs -- immune cells; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12687
• Languages: English
• ISSNs: 0902-4441

Abstract

Abstract: Long‐term therapy with IFN‐ α 2 is associated with sustained major molecular remissions in JAK2‐positive ET and PV. The efficacy of IFN‐ α 2 may be partly mediated by modulation of immune cells, which was investigated in twenty patients with ET ( n = 6) and PV ( n = 14). The frequency of CD4 + CD25 + Foxp3 + T cells was significantly increased during IFN‐ α 2 treatment in all patients ( P < 0.0001). A significant expansion of the CD56 bright NK cells ( P = 0.0002) and a concomitant decrease in the frequency of CD56 dim NK cells ( P < 0.0001) were also detected. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were studied in nine patients, and decreased frequencies of both cell types were observed during the course of treatment. On both mDCs and pDCs, HLA‐ABC expression was upregulated ( P = 0.003), but decreasing expression levels of HLA‐DR was detected on mDCs. The expression of CD40 ( P = 0.002), CD83 ( P = 0.03), and CD86 ( P = 0.01) increased, but was confined to pDCs. Furthermore, PD‐L1 expression was reduced on mDC ( P = 0.003) and increased on pDCs ( P = 0.02). No significant correlations were found between the changes in immune cells and hematological or molecular responses achieved in our cohort of patients. So forth, it remains to be revealed whether the profound changes in circulating immune cells contribute to the beneficial effects of long‐term IFN‐ α 2 treatment in some patients.