Ullah Md Ashik, Mackay Fabienne
Laboratory of B-Lymphocytes in Autoimmunity and Malignancies, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
The Department of Microbiology and Immunology, Faculty of Medicine, Dentistry and Health Sciences, School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Cancers (Basel). 2023 Mar 16;15(6):1791. doi: 10.3390/cancers15061791.
B cell-activating factor (BAFF; also known as CD257, TNFSF13B, BLyS) and a proliferation-inducing ligand (APRIL; also known as CD256, TNFSF13) belong to the tumor necrosis factor (TNF) family. BAFF was initially discovered as a B-cell survival factor, whereas APRIL was first identified as a protein highly expressed in various cancers. These discoveries were followed by over two decades of extensive research effort, which identified overlapping signaling cascades between BAFF and APRIL, controlling immune homeostasis in health and driving pathogenesis in autoimmunity and cancer, the latter being the focus of this review. High levels of BAFF, APRIL, and their receptors have been detected in different cancers and found to be associated with disease severity and treatment response. Here, we have summarized the role of the BAFF-APRIL system in immune cell differentiation and immune tolerance and detailed its pathogenic functions in hematological and solid cancers. We also highlight the emerging therapeutics targeting the BAFF-APRIL system in different cancer types.
B细胞激活因子（BAFF；也称为CD257、TNFSF13B、BLyS）和增殖诱导配体（APRIL；也称为CD256、TNFSF13）属于肿瘤坏死因子（TNF）家族。BAFF最初被发现是一种B细胞存活因子，而APRIL最初被鉴定为在各种癌症中高度表达的一种蛋白质。在这些发现之后，经过二十多年的广泛研究，确定了BAFF和APRIL之间重叠的信号级联，它们在健康状态下控制免疫稳态，并在自身免疫和癌症中推动发病机制，后者是本综述的重点。在不同癌症中检测到高水平的BAFF、APRIL及其受体，并发现它们与疾病严重程度和治疗反应相关。在这里，我们总结了BAFF-APRIL系统在免疫细胞分化和免疫耐受中的作用，并详细阐述了其在血液系统癌症和实体癌中的致病功能。我们还强调了针对不同癌症类型中BAFF-APRIL系统的新兴疗法。
