{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:45:05Z","timestamp":1790059505381,"version":"4.0.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-\u03b12. 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-\u03b12 (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 &lt; .0001).<\/jats:p>","DOI":"10.1182\/blood-2011-03-340992","type":"journal-article","created":{"date-parts":[[2011,6,27]],"date-time":"2011-06-27T22:49:44Z","timestamp":1309214984000},"page":"2170-2173","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":61,"title":["Increase in circulating CD4+CD25+Foxp3+ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-\u03b1"],"prefix":"10.1182","volume":"118","author":[{"given":"Caroline Hasselbalch","family":"Riley","sequence":"first","affiliation":[{"name":"Department of Hematology and"},{"name":"Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Krogh","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Hematology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Klinge","family":"Brimnes","sequence":"additional","affiliation":[{"name":"Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Carl","family":"Hasselbalch","sequence":"additional","affiliation":[{"name":"Department of Hematology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Weis","family":"Bjerrum","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per thor","family":"Straten","sequence":"additional","affiliation":[{"name":"Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Marie","family":"Svane","sequence":"additional","affiliation":[{"name":"Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Denmark;"},{"name":"Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"23","key":"2019111808342358600_B1","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1056\/NEJMra063728","article-title":"The myeloproliferative disorders.","volume":"355","author":"Campbell","year":"2006","journal-title":"N Engl J Med"},{"issue":"7037","key":"2019111808342358600_B2","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nature03546","article-title":"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.","volume":"434","author":"James","year":"2005","journal-title":"Nature"},{"issue":"17","key":"2019111808342358600_B3","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1056\/NEJMoa051113","article-title":"A gain-of-function mutation of JAK2 in myeloproliferative disorders.","volume":"352","author":"Kralovics","year":"2005","journal-title":"N Engl J Med"},{"issue":"4","key":"2019111808342358600_B4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ccr.2005.03.023","article-title":"Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.","volume":"7","author":"Levine","year":"2005","journal-title":"Cancer Cell"},{"issue":"6","key":"2019111808342358600_B5","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1600-0609.2007.00960.x","article-title":"The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis: impact on disease phenotype.","volume":"79","author":"Larsen","year":"2007","journal-title":"Eur J Haematol"},{"issue":"3","key":"2019111808342358600_B6","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1182\/blood-2006-12-064287","article-title":"Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia.","volume":"110","author":"Vannucchi","year":"2007","journal-title":"Blood"},{"issue":"7","key":"2019111808342358600_B7","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/leu.2008.113","article-title":"Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal.","volume":"22","author":"Vannucchi","year":"2008","journal-title":"Leukemia"},{"issue":"1","key":"2019111808342358600_B8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1365-2141.2009.08029.x","article-title":"Induction of complete remission of acute myeloid leukaemia by pegylated interferon-alpha-2a in a patient with transformed primary myelofibrosis.","volume":"149","author":"Berneman","year":"2010","journal-title":"Br J Haematol"},{"issue":"6","key":"2019111808342358600_B9","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1182\/blood-2006-03-009860","article-title":"High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a.","volume":"108","author":"Kiladjian","year":"2006","journal-title":"Blood"},{"issue":"8","key":"2019111808342358600_B10","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1182\/blood-2008-03-143537","article-title":"Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera.","volume":"112","author":"Kiladjian","year":"2008","journal-title":"Blood"},{"issue":"10","key":"2019111808342358600_B11","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00277-008-0498-4","article-title":"Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera.","volume":"87","author":"Larsen","year":"2008","journal-title":"Ann Hematol"},{"issue":"6","key":"2019111808342358600_B12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1179\/102453309X12473408860587","article-title":"Minimal residual disease and normalization of the bone marrow after long-term treatment with alpha-interferon2b in polycythemia vera: a report on molecular response patterns in seven patients in sustained complete hematological remission.","volume":"14","author":"Larsen","year":"2009","journal-title":"Hematology"},{"issue":"2","key":"2019111808342358600_B13","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00277-010-0993-2","article-title":"Complete molecular remission in a polycythaemia vera patient 12 years after discontinuation of interferon-alpha.","volume":"90","author":"Murphy","year":"2011","journal-title":"Ann Hematol"},{"issue":"32","key":"2019111808342358600_B14","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1200\/JCO.2009.23.6075","article-title":"Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera.","volume":"27","author":"Quintas-Cardama","year":"2009","journal-title":"J Clin Oncol"},{"issue":"11","key":"2019111808342358600_B15","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/nri1961","article-title":"Interferons, immunity and cancer immunoediting.","volume":"6","author":"Dunn","year":"2006","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"2019111808342358600_B16","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1177\/039463200702000218","article-title":"A novel unconventional antigen MPD5 elicits anti-tumor humoral immune responses in a subset of patients with polycythemia vera.","volume":"20","author":"Xiong","year":"2007","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"3","key":"2019111808342358600_B17","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.clim.2006.10.006","article-title":"Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.","volume":"122","author":"Xiong","year":"2007","journal-title":"Clin Immunol"},{"issue":"6\u20137","key":"2019111808342358600_B18","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.biochi.2007.04.006","article-title":"Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use.","volume":"89","author":"Ferrantini","year":"2007","journal-title":"Biochimie"},{"key":"2019111808342358600_B19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0065-230X(10)07003-X","article-title":"Regulatory T cells in cancer.","volume":"107","author":"Mougiakakos","year":"2010","journal-title":"Adv Cancer Res"},{"issue":"7","key":"2019111808342358600_B20","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nri2785","article-title":"FOXP3+ regulatory T cells in the human immune system.","volume":"10","author":"Sakaguchi","year":"2010","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"2019111808342358600_B21","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nri2037","article-title":"The dynamic co-evolution of memory and regulatory CD4+ T cells in the periphery.","volume":"7","author":"Akbar","year":"2007","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"2019111808342358600_B22","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1158\/0008-5472.CAN-08-3804","article-title":"FOXP3 defines regulatory T cells in human tumor and autoimmune disease.","volume":"69","author":"Kryczek","year":"2009","journal-title":"Cancer Res"},{"issue":"6","key":"2019111808342358600_B23","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.immuni.2009.03.019","article-title":"Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor.","volume":"30","author":"Miyara","year":"2009","journal-title":"Immunity"},{"issue":"2","key":"2019111808342358600_B24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.blre.2010.10.004","article-title":"JAK2 inhibitors: what's the true therapeutic potential?","volume":"25","author":"Santos","year":"2011","journal-title":"Blood Rev"},{"issue":"12","key":"2019111808342358600_B25","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa1002028","article-title":"Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.","volume":"363","author":"Verstovsek","year":"2010","journal-title":"N Engl J Med"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/118\/8\/2170\/1349113\/zh803411002170.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/118\/8\/2170\/1349113\/zh803411002170.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T08:58:08Z","timestamp":1574067488000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/118\/8\/2170\/29489\/Increase-in-circulating-CD4CD25Foxp3-T-cells-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,25]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,8,25]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2011-03-340992","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,25]]}}}