Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma
Abstract 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, suppressin...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82800-1 |
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| author | Shams ElDoha Galal ElDin Zaiema Heba Mohamed Saber Hafez Diaa El-Din Moussa Sherif Abou El-Ela Rawda Ahmed Alaaeldin Ahmed Mohamed Saad |
| author_facet | Shams ElDoha Galal ElDin Zaiema Heba Mohamed Saber Hafez Diaa El-Din Moussa Sherif Abou El-Ela Rawda Ahmed Alaaeldin Ahmed Mohamed Saad |
| author_sort | Shams ElDoha Galal ElDin Zaiema |
| collection | DOAJ |
| description | Abstract 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 + cytotoxic 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. |
| format | Article |
| id | doaj-art-9bbb1ca6aa234cb09691906979c8a835 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-9bbb1ca6aa234cb09691906979c8a8352025-01-19T12:20:38ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-82800-1Illuminating the impact of CD38-induced adenosine formation in B-cell lymphomaShams ElDoha Galal ElDin Zaiema0Heba Mohamed Saber Hafez1Diaa El-Din Moussa Sherif Abou El-Ela2Rawda Ahmed Alaaeldin Ahmed Mohamed Saad3Department of Clinical and Chemical Pathology, Ain shams UniversityDepartment of Haematology – Internal Medicine, Ain shams UniversityDepartment of Clinical Oncology and Nuclear Medicine, Ain shams UniversityDepartment of Clinical and Chemical Pathology, Ain shams UniversityAbstract 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 + cytotoxic 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.https://doi.org/10.1038/s41598-024-82800-1CD38 expressionExtracellular ADOMature B-cell lymphomaChronic lymphocytic leukemiaB-Non-Hodgkin lymphomaPD-1/PD-L1 axis |
| spellingShingle | Shams ElDoha Galal ElDin Zaiema Heba Mohamed Saber Hafez Diaa El-Din Moussa Sherif Abou El-Ela Rawda Ahmed Alaaeldin Ahmed Mohamed Saad Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma Scientific Reports CD38 expression Extracellular ADO Mature B-cell lymphoma Chronic lymphocytic leukemia B-Non-Hodgkin lymphoma PD-1/PD-L1 axis |
| title | Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma |
| title_full | Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma |
| title_fullStr | Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma |
| title_full_unstemmed | Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma |
| title_short | Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma |
| title_sort | illuminating the impact of cd38 induced adenosine formation in b cell lymphoma |
| topic | CD38 expression Extracellular ADO Mature B-cell lymphoma Chronic lymphocytic leukemia B-Non-Hodgkin lymphoma PD-1/PD-L1 axis |
| url | https://doi.org/10.1038/s41598-024-82800-1 |
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