{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:01:41Z","timestamp":1790020901626,"version":"4.0.1"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>\n                    The developmental timing of T cell generation imprints durable functional programs, yet how this shapes antitumor immunity remains unclear. Here, we combine genetic fate mapping with functional assays to dissect how thymic age and peripheral residency regulate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell behavior within the same host. We find that, compared with adulthood-derived CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, the adolescent-derived counterparts consistently exhibit enhanced tumor infiltration, increased effector cytokine production, and superior proliferative fitness. Transcriptomic and phenotypic profiling identify a CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    IL-18R\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    subset preferentially enriched among adolescent-derived T cells that shares core virtual memory-like features and displays elevated cytotoxic potential. Mechanistically, thymic origin timing and time spent in the periphery independently regulate the abundance and activity of this subset, revealing a two-tier control comprising developmental bias and postthymic remodeling. Functionally, CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    IL-18R\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells mediate potent tumor killing and confer robust therapeutic benefit in adoptive transfer models. Together, these findings establish developmental imprinting as an important determinant of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell heterogeneity and identify CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    IL-18R\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells as key effectors for antitumor immunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2612774123","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:05Z","timestamp":1790017925000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Thymic age and peripheral residence time determine antitumor competence of CD8\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1073","volume":"123","author":[{"given":"Yuanqin","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Wicki","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianpeng","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunrun","family":"Qu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Debo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berna","family":"Bou Tayeh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Wen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Hosseini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinnycius","family":"Pereira Almeida","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol S.","family":"Leung","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg A.","family":"Holl\u00e4nder","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Institute of Developmental and Regenerative Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02nhqek82","id-type":"ROR","asserted-by":"publisher"}],"name":"Pediatric Immunology, Department of Biomedicine, University of Basel and University Children\u2019s Hospital Basel","place":["Basel, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/05a28rw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biosystems Science and Engineering, Eidgen\u00f6ssische Technische Hochschule Zurich","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit Van den","family":"Eynde","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/022em3k58","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, de Duve Institute","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-1709","authenticated-orcid":false,"given":"Yang","family":"Shi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0180-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00649-5"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00927-z"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56221"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01960"},{"key":"e_1_3_4_9_2","first-page":"280","article-title":"Thymus size and age-related thymic involution: Early programming, sexual dimorphism, progenitors and stroma","volume":"3","author":"Gui J.","year":"2012","unstructured":"J. Gui, L. M. Mustachio, D. M. Su, R. W. Craig, Thymus size and age-related thymic involution: Early programming, sexual dimorphism, progenitors and stroma. Aging Dis. 3, 280\u2013290 (2012).","journal-title":"Aging Dis."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.02.010"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.029"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10242-y"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10243-x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.01.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811634116"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517246112"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.005"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl6322"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52230-8"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.10.013"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00990-3"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-025-01146-6"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05626-9"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","unstructured":"A. H. Long Fetal thymic expression defines the immunogenicity of tumor associated antigens. bioRxiv [Preprint] (2026). https:\/\/doi.org\/10.64898\/2026.01.25.701584 (Accessed 27 January 2026).","DOI":"10.64898\/2026.01.25.701584"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196509"},{"key":"e_1_3_4_28_2","unstructured":"Y. Yang Data from \u201cThymic age and peripheral residence time determine anti-tumor competence of CD8+ T cells.\u201d Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE339309. Deposited 20 July 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2612774123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:11Z","timestamp":1790017931000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2612774123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":28,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2026,9,29]]}},"alternative-id":["10.1073\/pnas.2612774123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2612774123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"assertion":[{"value":"2026-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2612774123"}}