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

TY - JOUR

T1 - 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

AU - Riley, Caroline H

AU - Brimnes, Marie K

AU - Hansen, Morten

AU - Jensen, Morten Krogh

AU - Hasselbalch, Hans K

AU - Kjaer, Lasse

AU - Straten, Per Thor

AU - Svane, Inge Marie

PY - 2016

Y1 - 2016

N2 - Long-term therapy with IFN-α2 is associated with sustained major molecular remissions in JAK2-positive ET and PV. The efficacy of IFN-α2 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-α2 treatment in all patients (P < 0.0001). A significant expansion of the CD56bright NK cells (P = 0.0002) and a concomitant decrease in the frequency of CD56dim 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-α2 treatment in some patients.

AB - Long-term therapy with IFN-α2 is associated with sustained major molecular remissions in JAK2-positive ET and PV. The efficacy of IFN-α2 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-α2 treatment in all patients (P < 0.0001). A significant expansion of the CD56bright NK cells (P = 0.0002) and a concomitant decrease in the frequency of CD56dim 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-α2 treatment in some patients.

KW - IFN-α treatment

KW - immune cells

KW - JAK2-positive MPNs

U2 - 10.1111/ejh.12687

DO - 10.1111/ejh.12687

M3 - Journal article

C2 - 26385526

AN - SCOPUS:84976336465

SN - 0902-4441

VL - 97

SP - 83

EP - 92

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 1

ER -