Cluster of differentiation 40 (CD40)–Cluster of differentiation 40 ligand (CD40L) and Cluster of differentiation 27 (CD27)–Cluster of differentiation 70 (CD70) costimulatory receptor–ligand pairs (CD40/CD40L and CD27/CD70)

The CD40–CD40L and CD27–CD70 pairs are critical costimulatory pathways within the tumor necrosis factor receptor superfamily (TNFRSF) that regulate the crosstalk between antigen-presenting cells (APCs) and T cells (UniProt P25942, P26842). CD40, expressed on dendritic cells (DCs) and B cells, interacts with CD40L (CD154) on activated T cells to "license" DCs, a process essential for the effective priming of CD8+ cytotoxic T lymphocytes (PubMed 29941550). Simultaneously, the CD27–CD70 axis provides a potent signal for T-cell expansion, survival, and the development of immunological memory (PubMed 30568240). In oncology, therapeutic strategies involve using agonistic monoclonal antibodies to trigger these receptors, thereby overcoming tumor-induced immunosuppression and enhancing the anti-tumor immune response. Conversely, blocking the CD40–CD40L interaction is a key approach in treating autoimmune diseases like systemic lupus erythematosus to inhibit pathogenic B-cell activation (PubMed 31515461). Safety considerations for these therapies include managing cytokine release syndrome and potential hepatotoxicity associated with systemic immune activation.

Other names

TNFRSF5-TNFSF5 and TNFRSF7-TNFSF7CD40-CD154 and CD27-CD70CD40-CD40L and CD27-CD70 pathwaysCostimulatory receptor-ligand pairs on APCs and T cells

Agonism of TNFRSF receptors (CD40, CD27) to enhance APC licensing and T-cell costimulation; antagonism of TNFSF ligands (CD40L, CD70) to block immune activation or induce antibody-dependent cellular cytotoxicity (ADCC).