Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses

In this study, we analysed the effects of OK432 on DC maturation, DC migration, cytokine and chemokine secretion as well as T-cell stimulatory capacity, and compared it to the cytokine cocktail alone and combinations of OK432 with the cytokine cocktail.OK432 induced a marked up-regulation of CD40 on the cell surface as well as a strong inflammatory response from the DC with significantly more secretion of 19 different cytokines and chemokines compared to the cytokine cocktail. Interestingly, secretion of IL-15 and IL-12p70 was detected at high concentrations after maturation of DC with OK432. However, the OK432 treated DC did not migrate as well as DC treated with cytokine cocktail in a transwell migration assay. During allogeneic T-cell stimulation OK432 treated DC induced proliferation of over 50 percent of CD4 and 30 percent of CD8 T-cells for more than two cell divisions, whereas cytokine cocktail treated DC induced proliferation of 12 and 11 percent of CD4 and CD8 T-cells, respectively.The clinically approved compound OK432 has interesting properties that warrants its use in DC immunotherapy and should be considered as a potential immunomodulating agent in cancer immunotherapy.Dendritic cells (DC) are a pivotal part of the immune system, bridging the innate and adaptive immune response. After receiving maturation stimuli such as inflammatory cytokines, direct T-cell stimulation or recognition of pathogen-associated molecular patterns (PAMP), the DC up-regulate the surface expression of major histocompatibility complex (MHC) class II as well as a number of co-stimulatory markers [1]. During maturation the DC shift role from antigen up-take to antigen presentation on MHC and migrate to secondary lymphoid organs where the DC stimulate T-cells with the appropriate T-cell receptor. Much work has been carried out to utilise the unique features of DC in clinical applications as ex vivo generation of DC has become standard practice [2,3]. Especially, their role in the