title: Increase in circulating CD4⁺CD25⁺Foxp3⁺ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α.
abstract: Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these patients. Foxp3(+) regulatory T cells play a pivotal role in maintaining immune homeostasis and, importantly, preventing immune reactivity to self-antigens; however, their suppressive activity can compromise an effective antitumor immune response, and high frequencies of regulatory T cells in peripheral blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4(+)CD25(+)Foxp3(+) T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN-α2 (13.0%; 95% confidence interval [CI] 10.8% to 15.2%) compared with healthy donors (6.1%; 95% CI 4.9% to 7.2%), patients with untreated chronic myeloproliferative neoplasms (6.9%; 95% CI 5.8% to 7.4%), or patients treated with hydroxyurea (5.8%; 95% CI 4.3% to 7.4%; P < .0001).
authors.affiliation: Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark. riley@dadlnet.dk
authors.forename: Caroline Hasselbalch
authors.initials: CH
authors.lastname: Riley
authors.forename: Morten Krogh
authors.initials: MK
authors.lastname: Jensen
authors.forename: Marie Klinge
authors.initials: MK
authors.lastname: Brimnes
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
authors.forename: Ole Weis
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
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000276:immunology*; D011087:Polycythemia Vera / Q000188:drug therapy / Q000276:immunology; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000276:immunology; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D011994:Recombinant Proteins; D006918:Hydroxyurea