title: 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.
abstract: 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 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-α2 treatment in some patients.
authors.affiliation: Department of Haematology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.|Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Riley
authors.affiliation: Institute for Inflammation Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Brimnes
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Department of Haematology, Roskilde Hospital, University of Copenhagen, Denmark.
authors.forename: Morten Krogh
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Department of Haematology, Roskilde Hospital, University of Copenhagen, Denmark.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hasselbalch
authors.affiliation: Department of Haematology, Roskilde Hospital, University of Copenhagen, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Kjaer
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per Thor
authors.initials: PT
authors.lastname: Straten
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D018925:Chemokines / Q000097:blood; D003062:Codon; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011087:Polycythemia Vera / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018925:Chemokines; D003062:Codon; D016898:Interferon-alpha; D053614:Janus Kinase 2
keywords: IFN-α treatment; JAK2-positive MPNs; immune cells