{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:41:02Z","timestamp":1791902462768,"version":"4.3.4"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD). We analyzed the immunophenotype from peripheral blood of these patients focusing on selected immune cell subsets (CD4+T cells, CD8+T cells,  T regulatory cells, NK cells, B-cells, monocytes, eosinophils, basophils, neutrophils) and serum levels of cytokines, chemokines and growth factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed higher number of leucocytes, in particular lymphocytes, B lymphopenia and lower number of T regulatory cells in TET patients with associated AD compared to TET patients without AD. In the group of TET patients with AD, we also observed increased serum levels of IL-15, VEGF, IP-10, GM-CSF, IL-6, and MIP-1\u03b1. Thus, we identified considerable differences in the lymphocyte profiles of TET patients with and without ADs, in particular a reduction in the numbers of B lymphocytes and T-regulatory cells in the former, as well as differences in the serum levels of various immune modulators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the pathogenic mechanisms are still unclear, our results add new knowledge to better understand the disease, suggesting the need of surveilling the immunophenotype of TET patients to ameliorate their clinical management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.908453","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T07:18:34Z","timestamp":1660807114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Immunological signature of patients with thymic epithelial tumors and Good syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Anna Maria","family":"Malfitano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"D\u2019Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"De Placido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Tortora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ottaviano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Pietroluongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Morra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitta","family":"Mucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Napolitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Montella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Giuliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabino","family":"De Placido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Terracciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovannella","family":"Palmieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Formisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv277","article-title":"Thymic epithelial tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","author":"Girard","year":"2015","journal-title":"Ann Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000663","article-title":"Introduction to the 2015 world health organization classification of tumors of the lung, pleura, thymus, and heart","volume":"10","author":"Travis","year":"2015","journal-title":"J Thorac Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181f20d9a","article-title":"The multidisciplinary approach to thymoma: combining molecular and clinical approaches","volume":"5","author":"Chau","year":"2010","journal-title":"J Thorac Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.revmed.2017.03.003","article-title":"[Thymoma and autoimmune diseases]","volume":"39","author":"Jamilloux","year":"2018","journal-title":"La Rev medecine interne"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2021.06.011","article-title":"Molecular landscape of thymic epithelial tumors","volume":"39","author":"Prays","year":"2022","journal-title":"Semin Diagn Pathol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2020.12.010","article-title":"Immunodeficiency and thymoma in good syndrome: Two sides of the same coin","volume":"231","author":"Guevara-Hoyer","year":"2021","journal-title":"Immunol letters"},{"key":"B7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/cmi.2010.74","article-title":"Thymoma and autoimmunity","volume":"8","author":"Shelly","year":"2011","journal-title":"Cell Mol Immunol"},{"key":"B8","first-page":"85","article-title":"Good's syndrome-association of the late onset combined immunodeficiency with thymoma: Review of literature and case report","volume":"17","author":"Tavakol","year":"2018","journal-title":"Iranian J allergy asthma Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2015.11.012","article-title":"Thymic epithelial tumor-associated cytopenia: A 10-year observational study in France","volume":"11","author":"Rivoisy","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ269","article-title":"Good syndrome: an adult-onset immunodeficiency remarkable for its high incidence of invasive infections and autoimmune complications","volume":"61","author":"Malphettes","year":"2015","journal-title":"Clin Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2009.207308","article-title":"Lichen planus in a case of good's syndrome (thymoma and immunodeficiency)","volume":"9","author":"Khan","year":"2009","journal-title":"Interactive Cardiovasc Thorac surgery"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.3184","article-title":"Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: An open-label phase II trial","volume":"37","author":"Cho","year":"2019","journal-title":"J Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12453","article-title":"A case of rheumatoid arthritis associated with hashimoto's thyroiditis and thymoma","volume":"20","author":"Zou","year":"2017","journal-title":"Int J rheumatic diseases"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezt567","article-title":"Thymoma and inter-relationships between clinical variables: a multicentre study in 537 patients","volume":"45","author":"Filosso","year":"2014","journal-title":"Eur J cardio-thoracic Surg"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000300","article-title":"Paraneoplastic disorders in thymoma patients","volume":"9","author":"Evoli","year":"2014","journal-title":"J Thorac Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.autrev.2015.09.005","article-title":"Thymoma associated with autoimmune diseases: 85 cases and literature review","volume":"15","author":"Bernard","year":"2016","journal-title":"Autoimmun Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.9.1044","article-title":"Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. a case report and review of the literature","volume":"39","author":"Boonen","year":"2000","journal-title":"Rheumatol (Oxford England)"},{"key":"B18","first-page":"1","article-title":"Thymectomy as treatment of autoimmune diseases other than myasthenia gravis","volume":"21","author":"D'Andrea","year":"1993","journal-title":"Thymus."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.679556","article-title":"When the good syndrome goes bad: A systematic literature review","volume":"12","author":"Shi","year":"2021","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.4081\/cp.2019.1112","article-title":"Good's syndrome, a rare form of acquired immunodeficiency associated with thymomas","volume":"9","author":"Tamburello","year":"2019","journal-title":"Clinics practice"},{"key":"B21","first-page":"31","article-title":"Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications","volume":"86","author":"Hermaszewski","year":"1993","journal-title":"Q J Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.01.006","article-title":"Good's syndrome remains a mystery after 55 years: A systematic review of the scientific evidence","volume":"135","author":"Kelesidis","year":"2010","journal-title":"Clin Immunol (Orlando Fla)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00005-012-0207-9","article-title":"Associated immunological disorders and cellular immune dysfunction in thymoma: a study of 87 cases from Thailand","volume":"61","author":"Thongprayoon","year":"2013","journal-title":"Archivum immunol therapiae experimentalis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2638","article-title":"Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma-associated b lymphopenia","volume":"101","author":"Masci","year":"2003","journal-title":"Blood."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.04.005","article-title":"Increase of circulating CD4+CD25+ T cells in myasthenia gravis patients with stability and thymectomy","volume":"112","author":"Sun","year":"2004","journal-title":"Clin Immunol (Orlando Fla)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20340","article-title":"Selective loss of regulatory T cells in thymomas","volume":"56","author":"Str\u00f6bel","year":"2004","journal-title":"Ann neurology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.03.011","article-title":"Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma","volume":"164","author":"Luther","year":"2005","journal-title":"J neuroimmunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1212\/WNL.0b013e3181f46fa5","article-title":"Undiminished regulatory T cells in the thymus of patients with myasthenia gravis","volume":"75","author":"Zhang","year":"2010","journal-title":"Neurology."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R","article-title":"Follow-up study of thymomas with special reference to their clinical stages","volume":"48","author":"Masaoka","year":"1981","journal-title":"Cancer."},{"key":"B30","doi-asserted-by":"publisher","first-page":"20793","DOI":"10.1038\/s41598-021-00190-0","article-title":"Cytokine signature and COVID-19 prediction models in the two waves of pandemics","volume":"11","author":"Cabaro","year":"2021","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2014.02.010","article-title":"Reference ranges of lymphocyte subsets in healthy adults and adolescents with special mention of T cell maturation subsets in adults of south Florida","volume":"219","author":"Valiathan","year":"2014","journal-title":"Immunobiology."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12804","article-title":"Phenotypical characterization of regulatory T cells in humans and rodents","volume":"185","author":"Rodr\u00edguez-Perea","year":"2016","journal-title":"Clin Exp Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1177\/039463201002300434","article-title":"Is hypogammaglobulinemia a constant feature in good's syndrome","volume":"23","author":"Federico","year":"2010","journal-title":"Int J immunopathol Pharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2011.12.022","article-title":"High prevalence of infections and autoimmunity in patients with thymoma","volume":"73","author":"Holbro","year":"2012","journal-title":"Hum Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3872","article-title":"Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease","volume":"96","author":"Hoffacker","year":"2000","journal-title":"Blood."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001221","article-title":"Exposure to IL-15 and IL-21 enables autoreactive CD8 T cells to respond to weak antigens and cause disease in a mouse model of autoimmune diabetes","volume":"186","author":"Ramanathan","year":"2011","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.04.003","article-title":"Interleukin-15: A new cytokine target for the treatment of inflammatory diseases","volume":"4","author":"McInnes","year":"2004","journal-title":"Curr Opin Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324545","article-title":"Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses","volume":"33","author":"R\u00fcckert","year":"2003","journal-title":"Eur J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12272","article-title":"Serum cytokine and chemokine profiles in patients with myasthenia gravis","volume":"176","author":"Uzawa","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2143","article-title":"Interleukin 15 provides relief to CTLs from regulatory T cell-mediated inhibition: implications for adoptive T cell-based therapies for lymphoma","volume":"19","author":"Perna","year":"2013","journal-title":"Clin Cancer Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100885","article-title":"B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients","volume":"187","author":"Schneider","year":"2011","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000931","article-title":"Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE","volume":"8","author":"Laurent","year":"2020","journal-title":"Neurology(R) Neuroimmunol Neuroinflamm"},{"key":"B43","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.coi.2018.09.002","article-title":"IL-6: a cytokine at the crossroads of autoimmunity","volume":"55","author":"Jones","year":"2018","journal-title":"Curr Opin Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06844.x","article-title":"Regulatory T cell-based immunotherapies in experimental autoimmune myasthenia gravis","volume":"1274","author":"Souroujon","year":"2012","journal-title":"Ann New York Acad Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.molimm.2021.02.011","article-title":"Imbalance of Th17 and tregs in thymoma may be a pathological mechanism of myasthenia gravis","volume":"133","author":"Chen","year":"2021","journal-title":"Mol Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040391","article-title":"IL-6: regulator of Treg\/Th17 balance","volume":"40","author":"Kimura","year":"2010","journal-title":"Eur J Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"6212410","DOI":"10.1155\/2018\/6212410","article-title":"Aberrant peripheral immune function in a good syndrome patient","volume":"2018","author":"Chen","year":"2018","journal-title":"J Immunol Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2007.05.003","article-title":"Immunohistochemical expression of vascular endothelial growth factor a (VEGF), and its receptors (VEGFR1, 2) in normal and pathologic conditions of the human thymus","volume":"190","author":"Cimpean","year":"2008","journal-title":"Ann Anat = Anatomischer Anzeiger"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.10.010","article-title":"Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases","volume":"13","author":"Antonelli","year":"2014","journal-title":"Autoimmun Rev"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01265","article-title":"Roles of GM-CSF in the pathogenesis of autoimmune diseases: An update","volume":"10","author":"Lotfi","year":"2019","journal-title":"Front Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071119","article-title":"GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival","volume":"205","author":"Sonderegger","year":"2008","journal-title":"J Exp Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-3-030-36667-4_2","article-title":"CCL3 signaling in the tumor microenvironment","volume":"1231","author":"Ntanasis-Stathopoulos","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0709517","article-title":"Infections and autoimmunity: the multifaceted relationship","volume":"87","author":"Sfriso","year":"2010","journal-title":"J leukocyte Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.908453\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T07:18:40Z","timestamp":1660807120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.908453\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,18]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2022.908453"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.908453","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,18]]},"article-number":"908453"}}