{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:59:13Z","timestamp":1776916753236,"version":"3.51.2"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005635","name":"Instituto Gulbenkian de Ci\u00eancia\u2013Funda\u00e7\u00e3o Calouste Gulbenkian","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005635","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/52435\/2013"],"award-info":[{"award-number":["SFRH\/BD\/52435\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/04555\/2013"],"award-info":[{"award-number":["UID\/Multi\/04555\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["CONGENTO"],"award-info":[{"award-number":["CONGENTO"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The thymus produces precursors of both conventional T cells (Tconv; also known as effector T cells) and regulatory T cells (Treg) whose interactions prevent autoimmunity while allowing efficient protective immune responses. Tumors express a composite of self-antigens and tumor-specific Ags and engage both Tconv and Treg. Along the aging process, the thymus involutes, and tumor prevalence increases, a correlation proposed previously to result from effector cell decline. In this work, we directly tested whether interruption of thymic activity in adult mice affects Foxp3-expressing Treg composition and function and alters tumor immune surveillance. Young adult mice, on two different genetic backgrounds, were surgically thymectomized (TxT) and analyzed or challenged 2 mo later. Cellular analysis revealed a 10-fold decrease in both Tconv and Treg numbers and a bias for activated cells. The persisting Treg displayed reduced stability of Foxp3 expression and, as a population, showed a compromised return to homeostasis upon induced perturbations. We next tested the growth of three tumor models from different tissue origins and\/or presenting distinct degrees of spontaneous immunogenicity. In none of these conditions, adult TxT facilitated tumor growth. Rather, TxT enhanced the efficacy of antitumor immunotherapies targeting Treg and\/or the immune checkpoint CTLA4, as evidenced by the increased frequency of responder mice and decreased intratumoral Treg to CD8+IFN-\u03b3+ cell ratio. Together, our findings point to a scenario in which abrogation of thymic activities affects preferentially the regulatory over the ridding arm of the immune activities elicited by tumors and argues that higher prevalence of tumors with age cannot be solely attributed to thymic output decline.<\/jats:p>","DOI":"10.4049\/jimmunol.2000626","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T10:20:12Z","timestamp":1611138012000},"page":"978-986","source":"Crossref","is-referenced-by-count":6,"title":["Interruption of Thymic Activity in Adult Mice Improves Responses to Tumor Immunotherapy"],"prefix":"10.1093","volume":"206","author":[{"given":"Jos\u00e9","family":"Almeida-Santos","sequence":"first","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , 2780-901 Oeiras ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0691-4308","authenticated-orcid":false,"given":"Marie-Louise","family":"Bergman","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , 2780-901 Oeiras ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3236-7435","authenticated-orcid":false,"given":"In\u00eas Amendoeira","family":"Cabral","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , 2780-901 Oeiras ,","place":["Portugal"]}]},{"given":"Jocelyne","family":"Demengeot","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia , 2780-901 Oeiras ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"2025030501570404900_r1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1600-065X.2011.01018.x","article-title":"Regulatory T cells and Foxp3","volume":"241","author":"Rudensky","year":"2011","journal-title":"Immunol. 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Sci."},{"key":"2025030501570404900_r4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.immuni.2004.07.009","article-title":"Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors","volume":"21","author":"Hsieh","year":"2004","journal-title":"Immunity"},{"key":"2025030501570404900_r5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1600-065X.2007.00487.x","article-title":"When three is not a crowd: a crossregulation model of the dynamics and repertoire selection of regulatory CD4+ T cells","volume":"216","author":"Carneiro","year":"2007","journal-title":"Immunol. Rev."},{"key":"2025030501570404900_r6","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.4049\/jimmunol.1001281","article-title":"Cutting edge: intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization","volume":"185","author":"Zelenay","year":"2010","journal-title":"J. Immunol."},{"key":"2025030501570404900_r7","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1073\/pnas.1221955110","article-title":"Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery","volume":"110","author":"Paiva","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030501570404900_r8","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190428","article-title":"Developmental and cellular age direct conversion of CD4+ T cells into ROR\u03b3+ or Helios+ colon Treg cells","volume":"217","author":"Pratama","year":"2020","journal-title":"J. Exp. Med."},{"key":"2025030501570404900_r9","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.jaci.2016.05.014","article-title":"Early thymectomy leads to premature immunologic ageing: an 18-year follow-up","volume":"138","author":"Gudmundsdottir","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030501570404900_r10","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/ni.3150","article-title":"Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors","volume":"16","author":"Thiault","year":"2015","journal-title":"Nat. Immunol."},{"key":"2025030501570404900_r11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/cr.2016.151","article-title":"Regulatory T cells in cancer immunotherapy","volume":"27","author":"Tanaka","year":"2017","journal-title":"Cell Res."},{"key":"2025030501570404900_r12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJMoa053007","article-title":"Prognostic significance of autoimmunity during treatment of melanoma with interferon","volume":"354","author":"Gogas","year":"2006","journal-title":"N. Engl. J. 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Autoimmun."},{"key":"2025030501570404900_r41","article-title":"Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy","volume":"12","author":"Silva","year":"2017","journal-title":"PLoS One"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/206\/5\/978\/61363254\/ji2000626.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/206\/5\/978\/61363254\/ji2000626.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:57:23Z","timestamp":1741121843000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/206\/5\/978\/7944164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2000626","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739406141.793583195","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.01.08.899484","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2021,3,1]]}}}