Cluster of differentiation 40 (CD40) (CD40)

Cluster of differentiation 40 (CD40) is a 48 kDa type I transmembrane glycoprotein and a member of the tumor necrosis factor receptor (TNFR) superfamily (UniProt: P25942). It is constitutively expressed on antigen-presenting cells (APCs), including alpha-type-1 polarized dendritic cells (alpha-DC1), which are specialized DCs optimized for high interleukin-12 (IL-12) production and potent induction of Th1 and cytotoxic T lymphocyte (CTL) responses (PubMed: 15123761). The interaction between CD40 and its ligand, CD154 (CD40L), is a fundamental licensing step that enables alpha-DC1s to effectively cross-present tumor antigens and activate anti-tumor immunity. In oncology, CD40 agonistic antibodies are developed to trigger this pathway independently of T-helper cells, thereby enhancing the efficacy of cancer vaccines and other immunotherapies (PubMed: 30633910). Conversely, blocking the CD40-CD154 axis is a therapeutic strategy for autoimmune diseases like lupus and rheumatoid arthritis, as well as for preventing organ transplant rejection. However, systemic CD40 activation is associated with significant safety challenges, including cytokine release syndrome and transient hepatotoxicity, necessitating careful dose optimization in clinical settings.

Other names

TNFRSF5B-cell surface antigen CD40CDW40p50Bp50Tumor necrosis factor receptor superfamily member 5

Agonism of the CD40 receptor to activate antigen-presenting cells and promote Th1-type immune responses; Antagonism of the CD40-CD154 interaction to suppress B-cell activation and inflammatory signaling.