One of the main functions of the CD40L/CD40 system is to activate and "license" DCs to prime effective cytotoxic CD8+ T cell responses. In brief, CD40 ligand (CD40L) expressed on CD4+ helper T cells engages CD40 on APCs and induces APC activation and maturation. In turn, such CD40-licensed APCs induce activation and proliferation of antigen-specific CD8+ cytotoxic T cells. In the absence of CD40L signalling, the interaction of CD8+ T cells with so-called "unlicensed" APCs induces T cell anergy or triggers formation of regulatory T cellS. Thus, CD4L0 is crucial for effective generation of cytotoxic CD8+ T cell immune responses. Although normally induced by helper T cells, CD40L signalling on APCs can also be effectively triggered using agonistic antibodies or CD40, thus bypassing the need for CD4+ T cell help . These features delineate a clear rationale for CD40 agonist-based cancer immunotherapy.
Brunekreeft KL, Strohm C, Gooden MJ, et al. Targeted delivery of CD40L promotes restricted activation of antigen-presenting cells and induction of cancer cell death. Molecular Cancer. 2014;13:85.