Adaptation to replating of dendritic cells synergizes with Toll-like receptor stimuli and enhances the pro-inflammatory cytokine profile.

Background: As initiators of the adaptive immune response, dendritic cells (DCs) can be used for anti-cancer immunotherapy. On addition of proper maturation stimuli DCs mature and produce pro-inflammatory cytokines that skew T cells in the direction needed for anti-cancer therapy. Further optimization of DC maturation might improve the efficacy of DCs for clinical application.

Monophosphoryl lipid A-induced pro-inflammatory cytokine expression does not require CD14 in primary human dendritic cells.

Objective: To elucidate if TLR4-mediated MyD88 and TRIF signalling by the clinically applicable Lipopolysaccharide (LPS)-derivative monophosphoryl lipid A (MPLA) in primary human dendritic cells requires LPS cofactors LPS-binding protein (LBP) and CD14.

Methods: Cytokine production by monocyte-derived DCs stimulated with MPLA or LPS was determined using ELISA. To investigate involvement of CD14 for action of LPS or MPLA, CD14 was inhibited using blocking antibodies or down-modulated using specific siRNA.

Comparison of media and serum supplementation for generation of monophosphoryl lipid A/interferon-γ-matured type I dendritic cells for immunotherapy.

Background Aims: Ex vivo-generated monocyte-derived dendritic cells (DCs) matured with monophosphoryl lipid A (MPLA) and interferon-γ (IFN-γ) can be used as cancer immunotherapy. MPLA/IFN-γ DCs induce Th1 T cell responses and have migratory capacity. Different culture regimens have been used for generation of immunotherapeutic DCs, with varying results.

TLR4-mediated pro-inflammatory dendritic cell differentiation in humans requires the combined action of MyD88 and TRIF.

TLR4 ligation can activate both the MyD88 and the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) signaling route. Whereas MyD88 is generally recognized as a universal adaptor for pro-inflammatory responses, TRIF is mainly thought to contribute to specific type I IFN responses. Here, we investigated the contribution of both MyD88 and TRIF to TLR4-mediated pro-inflammatory dendritic cell (DC) differentiation in human.