CD40–CD40 ligand (CD40L) interaction (CD40–CD40L)

The CD40–CD40 ligand (CD40L) interaction is a fundamental costimulatory pathway in the immune system (UniProt P25942, P29965). CD40 is a member of the tumor necrosis factor receptor superfamily expressed on antigen-presenting cells (APCs) like dendritic cells, while CD40L (CD154) is expressed on activated T cells (PubMed: 15123770). This interaction is crucial for "licensing" dendritic cells, enabling them to produce IL-12 and effectively prime cytotoxic T lymphocytes and Cytokine-Induced Killer (CIK) cells (PubMed: 25403713). In oncology, agonistic antibodies targeting CD40 are used to enhance anti-tumor immunity by activating DCs (PubMed: 30635337). Conversely, blocking this axis with antagonistic antibodies or decoy receptors is a strategy for treating autoimmune diseases like systemic lupus erythematosus and preventing graft rejection (PubMed: 28504025). A significant historical challenge in targeting CD40L was the risk of thromboembolism due to CD40L expression on platelets, which has led to the development of next-generation CD40-specific or Fc-modified agents (PubMed: 10931770).

Other names

CD40-CD154 interactionCD40-CD40LG interactionTNFRSF5-TNFSF5 interactionCD40-CD40L axisCD40 – CD40L interaction on dendritic cells and T/CIK cells

Therapeutic strategies involve either agonistic antibodies to CD40 to stimulate dendritic cell maturation and anti-tumor T-cell responses, or antagonistic antibodies/decoy receptors to CD40 or CD40L to inhibit costimulatory signaling in autoimmune and inflammatory diseases.