{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:33:42Z","timestamp":1789947222327,"version":"4.0.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,20]],"date-time":"2015-03-20T00:00:00Z","timestamp":1426809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0116723","type":"journal-article","created":{"date-parts":[[2015,3,20]],"date-time":"2015-03-20T19:23:34Z","timestamp":1426879414000},"page":"e0116723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Immune Derangements in Patients with Myelofibrosis: The Role of Treg, Th17, and sIL2R\u03b1"],"prefix":"10.1371","volume":"10","author":[{"given":"Jen C.","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Sindhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Kundra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad I.","family":"Kafeel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Lichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,3,20]]},"reference":[{"key":"ref1","first-page":"1151","article-title":"Immune complexes in myeloproliferative disorders","volume":"115","author":"CM Lewis","year":"1997","journal-title":"Lancet"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1365-2141.1978.tb01093.x","article-title":"Immune complexes in myelofibrosis: A possible guide to management","volume":"39","author":"CM Lewis","year":"1978","journal-title":"Br J Hematol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1182\/blood.V58.5.904.904","article-title":"Immunologic abnormalities in myelofibrosis with activation of the complement system","volume":"58","author":"BR Gordon","year":"1981","journal-title":"Blood"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00000441-196908000-00004","article-title":"Coombs\u2019 positive hemolytic anemia in myelofibrosis with myeloid metaplasia","volume":"258","author":"M Khumbanonda","year":"1969","journal-title":"Am J Med Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/00000441-197609000-00016","article-title":"Lupus anticoagulant in myelofibrosis","volume":"272","author":"B Bernhardt","year":"1976","journal-title":"Am J Med Sci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1182\/blood-2002-09-2928","article-title":"A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia","volume":"101","author":"RA Mesa","year":"2003","journal-title":"Blood"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ajh.21598","article-title":"Phase1\/-2 study of Pomalidomide in myelofibrosis","volume":"85","author":"RA Mesa","year":"2010","journal-title":"Am J Hematol"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1182\/blood-2006-02-004572","article-title":"Lenalidomide therapy in myelofibrosis with myeloid metaplasia","volume":"108","author":"A Tefferi","year":"2006","journal-title":"Blood"},{"key":"ref9","first-page":"4766","article-title":"Regulatory CD25<sup>+<\/sup>CD4<sup>+<\/sup> T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer","volume":"61","author":"EY Woo","year":"2001","journal-title":"Cancer Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/00002371-200301000-00009","article-title":"CD4<sup>+<\/sup>CD25<sup>+<\/sup> suppressor lymphocytes in the circulation of patients immunized against melanoma antigens","volume":"26","author":"LR Javia","year":"2003","journal-title":"J Immunother"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1002\/cncr.11618","article-title":"CD25<sup>+<\/sup>CD4<sup>+<\/sup> regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression","volume":"98","author":"T Sasada","year":"2003","journal-title":"Cancer"},{"key":"ref12","first-page":"4404","article-title":"Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers","volume":"9","author":"F Ichihara","year":"2003","journal-title":"Clin Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nm1093","article-title":"Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival","volume":"10","author":"TJ Curiel","year":"2004","journal-title":"Nat Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/sj.bjc.6602407","article-title":"Characteristics of CD25<sup>+<\/sup>CD4<sup>+<\/sup> regulatory T cells in the peripheral circulation of patients with head and neck cancer","volume":"92","author":"C Schaefer","year":"2005","journal-title":"Br J Cancer"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1158\/0008-5472.CAN-04-3232","article-title":"Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma","volume":"65","author":"LA Ormandy","year":"2005","journal-title":"Cancer Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1182\/blood-2003-07-2594","article-title":"Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma","volume":"103","author":"NA Marshall","year":"2004","journal-title":"Blood"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1158\/1078-0432.CCR-04-1869","article-title":"Outcome in Hodgkin\u2019s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells","volume":"11","author":"T Alvaro","year":"2005","journal-title":"Clin Cancer Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1182\/blood-2005-02-0642","article-title":"Reduced frequencies and suppressive function of CD4<sup>+<\/sup>CD25<sup>hi<\/sup> regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine","volume":"106","author":"M Beyer","year":"2005","journal-title":"Blood"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/sj.leu.2403907","article-title":"Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia","volume":"19","author":"M Motta","year":"2005","journal-title":"Leukemia"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1182\/blood-2005-08-3376","article-title":"Intratumoral CD4<sup>+<\/sup>CD25<sup>+<\/sup>-regulatory T-cell-mediated suppression of infiltrating CD4<sup>+<\/sup> T-cells in B-cell non-Hodgkin lymphoma","volume":"107","author":"ZZ Yang","year":"2006","journal-title":"Blood"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/j.1600-0609.2005.00537.x","article-title":"Increased population of CD4<sup>+<\/sup> D25<sup>high<\/sup>, regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients","volume":"75","author":"X Wang","year":"2005","journal-title":"Eur J Haematol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1182\/blood-2005-08-3101","article-title":"Dysfunctional T regulatory cells in multiple myeloma","volume":"107","author":"RH Prabhala","year":"2006","journal-title":"Blood"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1182\/blood-2007-01-067546","article-title":"CD4<sup>+<\/sup>CD25high Foxp3<sup>+<\/sup> regulatory T cells in myelodysplastic syndrome (MDS)","volume":"110","author":"SY Kordasti","year":"2007","journal-title":"Blood"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ni1181","article-title":"Natural regulatory T cells in infectious disease","volume":"6","author":"Y Belkaid","year":"2005","journal-title":"Nat Immunol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.smim.2003.12.007","article-title":"Regulatory T cells and organ transplantation","volume":"16","author":"H Waldmann","year":"2004","journal-title":"Semi in Immunol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1097\/00002281-200307000-00010","article-title":"Immune dysregulation, lyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis","volume":"15","author":"E Gambineri","year":"2003","journal-title":"Curr Opin Rheumatol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/1074-7613(95)90070-5","article-title":"Herpes virus Saimiri encodes a new cytokine,IL-17, which binds to a novel cytokine receptor","volume":"3","author":"Z Yao","year":"1995","journal-title":"Immunity"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nature01355","article-title":"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain","volume":"421","author":"DJ Cua","year":"2003","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1084\/jem.20030896","article-title":"Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation","volume":"198","author":"CA Murphy","year":"2003","journal-title":"J Exp Med"},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.bbrc.2008.07.060","article-title":"The prevalence of Th17 cells in patients with gastric cancer","volume":"374","author":"B Zhang","year":"2008","journal-title":"BiochemBiophys Res Commun"},{"issue":"40","key":"ref31","doi-asserted-by":"crossref","first-page":"15505","DOI":"10.1073\/pnas.0710686105","article-title":"Generation and regulation of human CD4<sup>+<\/sup> IL-17-producing T cells in ovarian cancer","volume":"105","author":"Y Miyahara","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cellimm.2011.03.026","article-title":"The number of CD161 positive Th17 cells are decreased in head and neck cancer patients","volume":"269","author":"R Kesselring","year":"2011","journal-title":"Cell Immunol"},{"issue":"2","key":"ref33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2249.2009.04011.x","article-title":"Increased frequencies of T helper type 17 cells in the peripheral blood of patients with acute myeloid leukaemia","volume":"158","author":"C Wu","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(08)60386-7","article-title":"Biology of the interleukin-2 receptor","volume":"70","author":"BH Nelson","year":"1998","journal-title":"Adv Immunol"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13547500701674063","article-title":"Serum soluble interleukin 2 receptor \u03b1 in human cancer of adult and children: A review","volume":"13","author":"E Bien","year":"2008","journal-title":"Biomarkers"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1365-2141.1994.tb04744.x","article-title":"Plasma soluble interleukin-2 receptor in patients with primary myelofibrosis","volume":"86","author":"JC Wang","year":"1994","journal-title":"Br J Haematol"},{"key":"ref37","first-page":"4766","article-title":"Regulatory CD4(<sup>+<\/sup>)CD25(<sup>+<\/sup>) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer","volume":"61","author":"EY Woo","year":"2001","journal-title":"Cancer Res"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Shakil SA, Chen C, Surahio A, Mirza,M, Su MY, et al (2010) T regulator cells (Treg) in patients with myelofibrosis. ASH annual meeting, Abstract #30076.","DOI":"10.1182\/blood.V116.21.5051.5051"},{"issue":"8","key":"ref39","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1182\/blood-2011-03-340992","article-title":"Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-\u03b1","volume":"118","author":"CH Riley","year":"2011","journal-title":"Blood"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0140-6736(89)90103-7","article-title":"Interleukin-2 receptor levels indicating relapse in multiple sclerosis","volume":"1","author":"K Adachi","year":"1989","journal-title":"Lancet"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/10428190500361029","article-title":"Aggressive non-Hodgkin\u2019s lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome","volume":"47","author":"E Fabre-Guillevin","year":"2006","journal-title":"Leuk Lymphoma"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1365-2567.2010.03308.x","article-title":"T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies","volume":"131","author":"CA Lindqvist","year":"2010","journal-title":"Immunology"},{"issue":"10","key":"ref43","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1182\/blood-2011-03-340885","article-title":"Soluble IL-2R\u03b1 facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma","volume":"118","author":"ZZ Yang","year":"2011","journal-title":"Blood"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.4049\/jimmunol.182.3.1541","article-title":"Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses","volume":"182","author":"LM Maier","year":"2009","journal-title":"J Immunol"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ajh.2830340411","article-title":"Idiopathic myelofibrosis: a clinical study of 80 patients","volume":"34","author":"H Hasselbalch","year":"1990","journal-title":"Am J Hematol"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.leukres.2013.09.001","article-title":"Increased prevalence of autoimmune phenomena in myelofibrosis: relationship with clinical and morphological characteristics, and with immunoregulatory cytokine patterns","volume":"37","author":"W Barcellini","year":"2013","journal-title":"Leuk Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"abstract 2837","DOI":"10.1182\/blood.V122.21.2837.2837","article-title":"Programmed Cell Death Receptor (PD-1), PD-1 Ligand (PD-L1) Expression and Myeloid Derived Suppressor Cells (MDSC) In Myeloid Neoplasms Implicate The Mechanism Of IMiD Treatment Of Myelofibrosis","author":"A Kundra","year":"2013","journal-title":"Blood"},{"issue":"9","key":"ref48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMoa1110557","article-title":"A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis","volume":"366","author":"S Verstovsek","year":"2012","journal-title":"N Engl J Med"},{"issue":"9","key":"ref49","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMoa1110556","article-title":"JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","volume":"366","author":"C Harrison","year":"2012","journal-title":"N Engl J Med"},{"issue":"10","key":"ref50","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1200\/JCO.2010.32.9490","article-title":"Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study","volume":"29","author":"A Tefferi","year":"2011","journal-title":"J Clin Oncol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"FS Hodi","year":"2010","journal-title":"N Engl J Med"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","volume":"26","author":"JR Brahmer","year":"2012","journal-title":"N Engl J Med"},{"issue":"26","key":"ref53","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"SL Topalian","year":"2012","journal-title":"N Engl J Med"},{"issue":"8","key":"ref54","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":"JJ Kiladjian","year":"2008","journal-title":"Blood"},{"issue":"32","key":"ref55","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":"A Quinta\u00b4s-Cardama","year":"2009","journal-title":"J Clin Oncol"},{"issue":"7","key":"ref56","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/blood-2013-03-484642","article-title":"The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo","volume":"122","author":"A Heine","year":"2013","journal-title":"Blood"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0116723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T23:23:10Z","timestamp":1717802590000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0116723"}},"subtitle":[],"editor":[{"given":"Deyu","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,20]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0116723","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,20]]}}}