The expanding role of APRIL in cancer and immunity

Proteins of the tumour necrosis factor (TNF) family are implicated in the regulation of essential cell processes such as proliferation, differentiation, survival and cell death. Altered expression of TNF family members is often associated with pathological conditions such as autoimmune disease and cancer. The TNF-like ligand APRIL (A PRoliferation Inducing Ligand), first described in 1998, was named for its capacity to stimulate tumour cell proliferation in vitro. APRIL expression was initially reported in haematopoietic cells in physiological conditions, and it is overexpressed in certain tumour tissues. APRIL is now known to be involved in activation and immune responses of B cells, as well as in B cell malignancies. This review focuses on recent advances in understanding APRIL and its receptors in physiology and tumour pathology, including the accumulating evidence that specific Toll-like receptor ligands can trigger APRIL-mediated responses, and the identification of new sources of APRIL such as epithelial cells and tumour-infiltrating neutrophils.