Dendritic cells (DCs) are considered to be the most potent antigen-presenting cells. Ever since the development of protocols for the in vitro generation of DCs, their application in immunotherapy against various malignancies has been explored. Even though the approach of using tumour antigen-presenting DCs in therapeutic vaccination strategies has been shown to work effectively in mice and look promising in in vitro studies, the actual clinical benefit for patients with cancer has been marginal. There clearly is still room for improvement. In this review, we will summarize recent clinical trials and findings and try to shed some light on the current status and the future of DC-based cancer immunotherapy.

Monocyte-derived dendritic cells (moDC) are an important scientific and clinical source of functional dendritic cells (DC). However, the optimization of the generation process has to date mainly been limited to the variation of soluble factors. In this study, we investigated the impact of the cell culture dish surface on phenotype and cytokine profile. We compared a standard cell culture dish to a non-adherent culture dish for two immunogenic maturation conditions, two tolerogenic conditions, and an unstimulated control. Phenotype, cytokine profile and T cell stimulatory capacity were determined after a 3-day culture. Light microscopy revealed an increase in homotypic cluster formation correlated with the use of non-adherent surfaces, which could be reduced by using blocking antibodies against CD18. All surface markers analyzed showed moderate to strong differences depending on the culture dish surface, including significantly decreased expression of key maturation markers such as CD80, CD86, and CCR7 as well as PD-L1 on cells stimulated with the Jonuleit cytokine cocktail cultured on a non-adherent surface. Significant differences in the secretion of many cytokines were observed, especially for cells stimulated with LPS, with over 10-fold decreased secretion of IL-10, IL12-p40, and TNF-α from the cells cultured on the non-adherent surface. All immunogenic moDC populations showed similar capacity to induce antigen-specific T cells. These results provide evidence that the DC phenotype depends on the surface used during moDC generation. This has important implications for the optimization of DC-based immunotherapy development and underlines that the local surrounding can interfere with the final DC population beyond the soluble factors.

Numerous trials using dendritic cell (DC)-based vaccinations for the treatment of cancer are being carried out. However, an improvement of the quality of DC used is highly warranted. We here generated human monocyte-derived dendritic cells using a 3 day protocol and stimulated the cells using a combination of OK432 (Picibanil), TLR7/8 ligand CL097, and reduced amounts of prostaglandin (PG)E. We analyzed phenotype, migratory, and T-cell stimulatory capacity compared to a cytokine cocktail consisting of IL-1β, IL-6, TNF, and PGE. The OK432 cocktail stimulated cells had a similar mature phenotype with upregulated co-stimulatory molecules, HLA-DR and CCR7 as the cytokine cocktail-matured cells and a similar cytokine profile except increased amounts of IL-12p70. Chemotaxis towards CCL19 was reduced compared to the cytokine cocktail, but increased compared to OK432 alone. The T-cell stimulatory capacity was similar to the cytokine cocktail stimulated cells. In conclusion, the OK432 cocktail has the advantage of inducing IL-12p70 production without impairing phenotype or T-cell stimulatory capacity of the cells and might, therefore, be an advantageous alternative to be used in DC-based immunotherapy.