{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:30:55Z","timestamp":1788474655107,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T00:00:00Z","timestamp":1656201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leukemia and Lymphoma Society of Canada","award":["431124"],"award-info":[{"award-number":["431124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The ecto-nucleotidase CD73 is an important immune checkpoint in tumor immunity that cooperates with CD39 to hydrolyze pro-inflammatory extracellular ATP into immunosuppressive adenosine. While the role of CD73 in immune evasion of solid cancers is well established, its role in leukemia remains unclear. To investigate the role of CD73 in the pathogenesis of chronic lymphocytic leukemia (CLL), E\u00b5-TCL1 transgenic mice that spontaneously develop CLL were crossed with CD73\u2212\/\u2212 mice. Disease progression in peripheral blood and spleen, and CLL markers were evaluated by flow cytometry and survival was compared to CD73-proficient E\u00b5-TCL1 transgenic mice. We observed that CD73 deficiency significantly delayed CLL progression and prolonged survival in E\u00b5-TCL1 transgenic mice, and was associated with increased accumulation of IFN-\u03b3+ T cells and effector-memory CD8+ T cells. Neutralizing IFN-\u03b3 abrogated the survival advantage of CD73-deficient E\u00b5-TCL1 mice. Intriguingly, the beneficial effects of CD73 deletion were restricted to male mice. In females, CD73 deficiency was uniquely associated with the upregulation of CD39 in normal lymphocytes and sustained high PD-L1 expression on CLL cells. In vitro studies revealed that adenosine signaling via the A2a receptor enhanced PD-L1 expression on E\u00b5-TCL1-derived CLL cells, and a genomic analysis of human CLL samples found that PD-L1 correlated with adenosine signaling. Our study, thus, identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway.<\/jats:p>","DOI":"10.3390\/cancers14133130","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"3130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CD73 Promotes Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-8161","authenticated-orcid":false,"given":"David","family":"Allard","sequence":"first","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Facult\u00e9 de Pharmacie, l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Chrobak","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7208-6494","authenticated-orcid":false,"given":"Yacine","family":"Bareche","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Facult\u00e9 de Pharmacie, l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Allard","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Tessier","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie A.","family":"Bergeron","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Facult\u00e9 de Pharmacie, l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Jewish General Hospital, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Stagg","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Institut du Cancer de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"Facult\u00e9 de Pharmacie, l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40164-020-00170-6","article-title":"Leukemia incidence trends at the global, regional, and national level between 1990 and 2017","volume":"9","author":"Dong","year":"2020","journal-title":"Exp. 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