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Review
. 2023 Mar 16;15(6):1791.
doi: 10.3390/cancers15061791.

The BAFF-APRIL System in Cancer

Md Ashik Ullah  1 , Fabienne Mackay  1   2   3   4
Affiliations
Review

The BAFF-APRIL System in Cancer

Md Ashik Ullah et al. Cancers (Basel). .

Abstract

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.

Keywords: APRIL; B Cell; BAFF; BAFF-R; BCMA; TACI; hematological cancers; solid cancers.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of BAFF and APRIL on immune homeostasis. BAFF and APRIL are produced by immune and non-immune cells; however, the expression of the cognate receptors is restricted to specific immune cells. BAFF-APRIL binding with their corresponding receptors regulates cell differentiation, proliferation, survival, and effector functions.
Figure 2
Figure 2
Role of the BAFF-APRIL system in the development of hematological cancers. Dysregulated BAFF-APRIL signaling primarily contributes to the proliferation and survival of cancer cells, outlined in this schematic, with the mechanisms of action described in the relevant sections. Abbreviations: B-ALL = B-cell acute lymphoblastic leukemia; GC B cells = germinal center B cells; HRS cells = Hodgkin and Reed–Sternberg cells; HL = Hodgkin’s lymphoma; PC = plasma cells; MM cells = multiple myeloma cells; Fo B cells = follicular B cells; Burkitt’s Lymphoma; CLL = chronic lymphocytic leukemia; MBL = monoclonal B-cell lymphocytosis; TME = tumor microenvironment; CNSL = central nervous system lymphoma; DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; HCL = hairy cell leukemia; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma. ↑ refers to upregulation and ↓ refers to downregulation.
Figure 3
Figure 3
Role of the BAFF-APRIL system in the development of solid cancers. Dysregulated BAFF-APRIL signaling primarily contributes to the proliferation and survival of solid tumors, outlined in this schematic. The mechanisms of action are described in the relevant sections. Abbreviations: TME = tumor microenvironment; HCC = hepatocellular carcinoma. ↑ refers to upregulation and ↓ refers to downregulation.
See this image and copyright information in PMC

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