Zaiema Shams ElDoha Galal ElDin, Hafez Heba Mohamed Saber, El-Ela Diaa El-Din Moussa Sherif Abou, Saad Rawda Ahmed Alaaeldin Ahmed Mohamed
Department of Clinical and Chemical Pathology, Ain shams University, Cairo, Egypt.
Department of Haematology - Internal Medicine, Ain shams University, Cairo, Egypt.
Sci Rep. 2025 Jan 13;15(1):1807. doi: 10.1038/s41598-024-82800-1.
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.
癌细胞中CD38的表达可能通过产生细胞外腺苷（ADO）介导免疫抑制作用，该腺苷通过细胞成分和肿瘤细胞上的G蛋白偶联细胞表面受体发挥作用。这会增加PD-1的表达及其与PD-L1的相互作用，从而抑制CD8+细胞毒性T细胞。本研究探讨了CD38表达升高和细胞外ADO对成熟B细胞淋巴瘤患者各种血液学和临床参数的影响，以及它们与PD-1/PD-L1轴可溶性对应物的相关性。我们对90例成熟B细胞淋巴瘤患者进行了研究，这些患者根据流式细胞术检测分为CD38阳性和CD38阴性，成熟B细胞淋巴瘤又分为慢性淋巴细胞白血病（CLL）和B细胞非霍奇金淋巴瘤（B-NHL）亚型。使用夹心ELISA法检测他们的血清ADO、可溶性PD-1和PD-L1水平。我们的研究显示，成熟B细胞淋巴瘤患者中CD38表达、sADO、sPD-1和sPD-L1之间呈正相关。CD38阳性患者的sADO、sPD-1和sPD-L1水平更高。CD38表达升高和细胞外ADO对成熟B细胞淋巴瘤患者的血红蛋白（HB）水平和血小板（PLT）计数有负面影响，且与更高的风险分层呈正相关。本研究探讨了CD38表达和细胞外ADO升高对B细胞淋巴瘤的潜在影响及其与PD-1/PD-L1轴的联系。我们的研究结果强调了细胞外ADO对成熟B细胞淋巴瘤肿瘤形成过程的影响。我们还建议靶向CD38诱导的ADO形成途径，这可能成为成熟B细胞肿瘤中有多方面作用的有前景的治疗性免疫靶点。
