{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T23:40:32Z","timestamp":1736811632938,"version":"3.33.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The expression of CD38 by cancer cells may mediate an immune-suppressive effect by producing Extracellular Adenosine (ADO) acting through G-protein-coupled cell surface receptors on cellular components and tumor cells. This can increase PD-1 expression and interaction with PD-L1, suppressing CD8\u2009+\u2009cytotoxic T cells. This study examines the impact of heightened CD38 expression and extracellular ADO on various hematological and clinical parameters in patients with mature B-cell lymphoma, alongside their correlation with the soluble counterparts of the PD-1\/PD-L1 axis. Our study was conducted on 90 patients, CD38-positive and CD38-negative (measured by flow cytometry), with mature B-cell lymphoma divided into CLL and B-NHL subtypes. Their serum ADO, soluble PD-1, and PD-L1 levels were measured using a sandwich ELISA. Our study revealed a positive correlation between CD38 expression, sADO, sPD-1, and sPD-L1 in mature B-cell lymphoma patients. CD38-positive patients had higher sADO, sPD-1, and sPD-L1 levels. Higher CD38 expression and extracellular ADO negatively affected HB level and PLT count and positively correlated with the higher risk stratification in mature B-cell lymphoma patients. This study explored the potential impact of CD38 expression and elevated extracellular ADO on B-cell lymphoma alongside their link with the PD-1\/PD-L1 axis. Our findings underscore the influence of extracellular ADO on the neoplastic process of mature B-cell lymphoma. We also propose targeting the CD38-induced-ADO formation pathway, which could serve as a promising therapeutic immune target with multifaceted effects within mature B-cell neoplasms.<\/jats:p>","DOI":"10.1038\/s41598-024-82800-1","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T10:35:01Z","timestamp":1736764501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7046-6146","authenticated-orcid":false,"given":"Shams ElDoha Galal ElDin","family":"Zaiema","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba Mohamed Saber","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diaa El-Din Moussa Sherif Abou","family":"El-Ela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0935-6380","authenticated-orcid":false,"given":"Rawda Ahmed Alaaeldin Ahmed Mohamed","family":"Saad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"issue":"1","key":"82800_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41375-022-01764-1","volume":"37","author":"B Falini","year":"2023","unstructured":"Falini, B., Martino, G. & Lazzi, S. A comparison of the international consensus and 5th world health organization classifications of mature B-cell lymphomas. Leukemia 37(1), 18\u201334 (2023).","journal-title":"Leukemia"},{"issue":"4","key":"82800_CR2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrclinonc.2016.168","volume":"14","author":"A Goodman","year":"2017","unstructured":"Goodman, A., Patel, S. P. & Kurzrock, R. PD-1\u2013PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat. Reviews Clin. Oncol. 14(4), 203\u2013220 (2017).","journal-title":"Nat. Reviews Clin. Oncol."},{"key":"82800_CR3","doi-asserted-by":"crossref","unstructured":"Garcia-Lacarte, M., Grijalba, S. C., Melchor, J., Arnaiz-Lech\u00e9, A., & Roa, S. The PD-1\/PD-L1 checkpoint in normal germinal centers and diffuse large B-cell lymphomas. Cancers 13(18), 4683. 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Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol. Rev. 270(1), 95\u2013112 (2016).","journal-title":"Immunol. Rev."},{"key":"82800_CR10","doi-asserted-by":"crossref","unstructured":"Saltarella, I. et al. Mechanisms of resistance to anti-CD38 daratumumab in multiple myeloma. Cells 9(1), 167 (2020).","DOI":"10.3390\/cells9010167"},{"key":"82800_CR11","doi-asserted-by":"crossref","unstructured":"Costa, F., Marchica, V., Storti, P., Malavasi, F. & Giuliani, N. PD-L1\/PD-1 axis in multiple myeloma microenvironment and a possible link with CD38-mediated immune-suppression. Cancers 13(2), 164. (2021).","DOI":"10.3390\/cancers13020164"},{"key":"82800_CR12","doi-asserted-by":"crossref","unstructured":"Garcia-Gil, M., Camici, M., Allegrini, S., Pesi, R., & Tozzi, M. Metabolic aspects of adenosine functions in the brain. Front. Pharmacol. 12, 672182 (2021).","DOI":"10.3389\/fphar.2021.672182"},{"key":"82800_CR13","unstructured":"Mikdar, M. et al. 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All methods were carried out according to the guidelines and rules of the ethical committee of Ain Shams University (ASU). All experimental protocols were approved by the ethical committee regulations of Ain Shams University (ASU).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"1807"}}