CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in
activation of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells capable of initiating cytotoxic
T-lymphocyte immune response against cancer cells. However, there are few studies on the characterization of DCs in
cancer, specifically their expression of CD40, despite its implication in cancer immunotherapy. We reviewed available
data on the expression of CD40 on DCs in various cancers, and its implications for cancer immunotherapy.
A systematic review on CD40 expression on DCs in cancer was performed with reference to preferred reporting items for
systematic reviews and meta-analyses (PRISMA). Studies that satisfied the inclusion and exclusion criteria were 21 out of 927.
Variations in type and status of the cancers, source of DCs and methodology for detecting CD40 expression amongst the
studies resulted in contrasting results. DCs generally expressed low CD40 in tumor infiltrating DCs (tiDCs), in DCs
derived by in vitro culture from blood monocytes using cytokine stimulation (MoDCs) and in DCs exposed in vitro to
tumor cells lines; the studies suggested that CD40 expression in DCs is impaired in cancer particularly in metastatic
disease. However, DCs identified in fresh peripheral blood mononuclear cells (PBMC) expressed higher numbers of
CD40 positive cells in some cancer patients, which could be due to tumor-derived factors leading to partially-stimulated
DCs. The results provide evidence that some cancer patients may show partial systemic DC activation and expression of
increased CD40 in response to the presence of tumor but that such activity may become abortive in the presence of factors
produced by the tumor.
This review has thus identified key papers on CD40 expression on DCs in various cancers and discusses the limitations
and contrasting results of these studies in relation to variations in methodology. The results highlight the need for further
studies on the role of CD40-CD40 ligand pathway to inform cancer treatment.