{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:11:48Z","timestamp":1792498308915,"version":"4.5.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Michelle Cadorette Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Thymic epithelial tumors (TETs) are rare tumors for which treatment options are limited. The ongoing need for improved systemic therapies reflects a limited understanding of tumor biology as well as the normal thymus. The essential role of the thymus in adaptive immunity is largely effected by its epithelial compartment, which directs thymocyte (T-cell) differentiation and immunologic self-tolerance. With aging, the thymus undergoes involution whereby epithelial tissue is replaced by adipose and other connective tissue, decreasing immature T-cell production. Against this natural drive toward involution, a fraction of thymuses will instead undergo oncologic transformation, leading to the formation of TETs, including thymoma and thymic carcinoma. The rarity of these tumors restricts investigation of the mechanisms of tumorigenesis and development of rational treatment options. To this end, the development of technologies which allow deep molecular profiling of individual tumor cells permits a new window through which to view normal thymic development and contrast the malignant changes that result in oncogenic transformation. In this review, we describe the findings of recent illuminating studies on the diversity of cell types within the epithelial compartment through thymic differentiation and aging. We contextualize these findings around important unanswered questions regarding the spectrum of known somatic tumor alterations, cell of origin, and tumor heterogeneity. The perspectives informed by single-cell molecular profiling offer new approaches to clinical and basic investigation of thymic epithelial tumors, with the potential to accelerate development of improved therapeutic strategies to address ongoing unmet needs in these rare tumors.<\/jats:p>","DOI":"10.1093\/oncolo\/oyae046","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T21:02:36Z","timestamp":1711227756000},"page":"473-483","source":"Crossref","is-referenced-by-count":11,"title":["Single-Cell Sequencing Illuminates Thymic Development: An Updated Framework for Understanding Thymic Epithelial Tumors"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-8579","authenticated-orcid":false,"given":"Christopher S","family":"Nabel","sequence":"first","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital , Boston, MA , USA"},{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne B","family":"Ackman","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Department of Radiology, Massachusetts General Hospital , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1591","authenticated-orcid":false,"given":"Yin P","family":"Hung","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Department of Pathology, Massachusetts General Hospital , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Abner","family":"Louissaint","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Department of Pathology, Massachusetts General Hospital , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J","family":"Riely","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"2024060305562671900_CIT0001","first-page":"e0227197","article-title":"Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States","volume-title":"PLoS One","author":"Hsu","year":"2020"},{"key":"2024060305562671900_CIT0002","first-page":"875","article-title":"The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes","volume-title":"Autoimmun Rev","author":"Marx","year":"2013"},{"key":"2024060305562671900_CIT0003","first-page":"436","article-title":"Paraneoplastic syndromes and thymic malignancies: an examination of the international thymic 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