{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:59:19Z","timestamp":1790067559785,"version":"4.0.1"},"posted":{"date-parts":[[2026,1,27]]},"group-title":"Immunology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["U19 AI057229"],"award-info":[{"award-number":["U19 AI057229"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P01 AI153559"],"award-info":[{"award-number":["P01 AI153559"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00yt0ea73","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04n65rp89","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01f6q3121","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Tumor associated antigens (TAAs) are promising targets for cancer immunotherapy, yet their immunogenicity varies widely and remains poorly understood. Here, we show that the immunogenic potential of TAAs is largely shaped by their expression in the thymus, likely established during fetal development. By integrating single-cell transcriptomic data across fetal and postnatal thymic epithelial cells (TECs), we find that TAA expression in fetal TECs predicts both\n                  <jats:italic>in vitro<\/jats:italic>\n                  CD8\u207a T cell immunogenicity and the immune pressure against TAAs that occurs clinically in patients treated with immune checkpoint inhibitors. Notably, CD8\u207a T cells recognizing TAAs highly expressed in the fetal thymus exhibit attenuated transcriptional, signaling, and metabolic responses even in the na\u00efve state, consistent with a tolerogenic imprinting imparted during thymic development and selection. Further, fetal thymic expression of TAAs can be leveraged to prioritize candidate targets for therapeutic use. These findings provide a biologic basis for the extreme variability seen in TAA immunogenicity and define guiding principles for rational antigen selection to drive the next generation of effective TAA-targeted immunotherapies.\n                <\/jats:p>","DOI":"10.64898\/2026.01.25.701584","type":"posted-content","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:45:20Z","timestamp":1769525120000},"source":"Crossref","is-referenced-by-count":1,"title":["Fetal Thymic Expression Defines the Immunogenicity of Tumor Associated Antigens"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-9095","authenticated-orcid":false,"given":"Adrienne H.","family":"Long","sequence":"first","affiliation":[{"name":"Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn R.","family":"Tooker","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Pathoulas","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Beppler","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Bilich","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu","family":"Shankar","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"Bracey","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020503340852000_2026.01.25.701584v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"2026020503340852000_2026.01.25.701584v1.2","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1016\/j.cell.2025.06.019","article-title":"A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma","volume":"188","year":"2025","journal-title":"Cell"},{"key":"2026020503340852000_2026.01.25.701584v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01786-3"},{"key":"2026020503340852000_2026.01.25.701584v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12213"},{"key":"2026020503340852000_2026.01.25.701584v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature25480"},{"key":"2026020503340852000_2026.01.25.701584v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0387-x"},{"key":"2026020503340852000_2026.01.25.701584v1.7","unstructured":"Apavaloaei, A. et al. 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