{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:09Z","timestamp":1790709609853,"version":"4.1.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"88","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,10,27]]},"abstract":"<jats:p>\n            In chronic infections and cancer, T cells are exposed to prolonged antigen stimulation, resulting in loss of function (or exhaustion) and impairment of effective immunological protection. Exhausted T cells are heterogeneous and include early progenitors (Tpex) and terminally exhausted cells (Tex). Here, we used bulk and single-cell transcriptomics to analyze expression of transposable elements (TEs) in subpopulations of mouse and human CD8\n            <jats:sup>+<\/jats:sup>\n            tumor-infiltrating T lymphocytes (TILs). We show that in mice, members of the virus-like murine VL30 TE family (mostly intact, evolutionary young ERV1s) are strongly repressed in terminally exhausted CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in both tumor and viral models of exhaustion. Tpex expression of these VL30s, which are mainly intergenic and transcribed independently of their closest gene neighbors, was driven by Fli1, a transcription factor involved in progression from Tpex to Tex. Immune checkpoint blockade (ICB) in both mice and patients with cancer increased TE expression (including VL30 in mice), demonstrating that TEs may be applicable as ICB response biomarkers. We conclude that expression of TEs is tightly regulated in TILs during establishment of exhaustion and reprogramming by ICB. Analyses of TE expression on single cells and bulk populations open opportunities for understanding immune cell identity and heterogeneity, as well as for defining cellular gene expression signatures and disease biomarkers.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adf8838","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T17:59:36Z","timestamp":1698429576000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":19,"title":["Selective control of transposable element expression during T cell exhaustion and anti\u2013PD-1 treatment"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-5826","authenticated-orcid":true,"given":"Pierre-Emmanuel","family":"Bont\u00e9","sequence":"first","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-5981","authenticated-orcid":true,"given":"Christina","family":"Metoikidou","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-3829","authenticated-orcid":true,"given":"Sandrine","family":"Heurtebise-Chretien","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4434-3075","authenticated-orcid":true,"given":"Yago A.","family":"Arribas","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-1472","authenticated-orcid":true,"given":"Aur\u00e9lien","family":"Sutra Del Galy","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1988-4358","authenticated-orcid":true,"given":"Mengliang","family":"Ye","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Laura","family":"Niborski","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Zueva","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-8442","authenticated-orcid":true,"given":"Eliane","family":"Piaggio","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-4433","authenticated-orcid":true,"given":"Agathe","family":"Seguin-Givelet","sequence":"additional","affiliation":[{"name":"Institut Mutualiste Montsouris, Paris 75014, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."},{"name":"Institut Curie, Institut du Thorax Curie Montsouris, Paris 75005, France."},{"name":"Paris Saclay, UVSQ, UFR Simmone Veil, Versailles 78000, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-7445","authenticated-orcid":true,"given":"C\u00e9cile","family":"Alanio","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."},{"name":"Laboratoire d'immunologie clinique, Institut Curie, Paris 75005, France."},{"name":"Parker Institute of Cancer Immunotherapy, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-2608","authenticated-orcid":true,"given":"Marianne","family":"Burbage","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-2314","authenticated-orcid":true,"given":"Christel","family":"Goudot","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-8416","authenticated-orcid":true,"given":"Sebastian","family":"Amigorena","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris 75005, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.09.013"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.10.008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0235-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.04.014"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.10.009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01224-z"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abh0272"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31504-z"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(89)90039-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2165"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ympev.2015.03.009"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1629"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.05.005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600545"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06008"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014660108"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.04.004"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08858"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2008511"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08674"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.35"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.011"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5497"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.080663.108"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.218149.116"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912008117"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13100-016-0066-8"},{"key":"e_1_3_2_30_2","article-title":"Origins and function of VL30 lncRNA packaging in small extracellular vesicles: Implications for cellular physiology and pathology","volume":"9","author":"Mantziou S.","year":"2021","unstructured":"S.\u00a0Mantziou, G. S.\u00a0Markopoulos, Origins and function of VL30 lncRNA packaging in small extracellular vesicles: Implications for cellular physiology and pathology. 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Bonte M.\u00a0Ye T.\u00a0Hoyler M.\u00a0Gentili N.\u00a0Burgdorf S.\u00a0Durand F.\u00a0Aprahamian G.\u00a0Kroemer N.\u00a0Manel J.\u00a0J.\u00a0Waterfall R.\u00a0Milne C.\u00a0Goudot G.\u00a0J.\u00a0Towers S.\u00a0Amigorena Induction of transposable element expression is central to innate sensing. bioRxiv 069187 [Preprint]. 11 September 2021. https:\/\/doi.org\/10.1101\/2021.09.10.457789.","DOI":"10.1101\/2021.09.10.457789"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00989-7"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq7871"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.adf8838","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T13:09:51Z","timestamp":1705410591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adf8838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":51,"journal-issue":{"issue":"88","published-print":{"date-parts":[[2023,10,27]]}},"alternative-id":["10.1126\/sciimmunol.adf8838"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.adf8838","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,27]]},"assertion":[{"value":"2022-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadf8838"}}