Dendritic Cell-Based Tumor Vaccines and Antigen Presentation Attenuators

Abstract

Dendritic cell (DC)-based tumor vaccines are being extensively tested to treat cancer patients. Although the results of most DC-based clinical trials have been disappointing, recent advances in the basic molecular understanding of positive and negative regulation of antigen presentation and immune responses can form a basis to enhance the efficacy of DC-based vaccines. Here we describe the new understanding of the importance of Toll-like receptor, tumor necrosis factor receptor, and cytokine receptor signaling in activation of innate and adaptive immunity. In particular, we describe the emerging importance of hardwired negative regulators, such as cytokine signaling regulators, as antigen presentation attenuators (APAs), providing a new strategy to break self-tolerance and enhance the potency of tumor vaccines by inhibiting APAs.

Plasmacytoid Dendritic Cells Synergize with Myeloid Dendritic Cells in the Induction of Antigen-Specific Antitumor Immune Responses

“…Recent studies have shown that strong innate immunity is required to develop a potent adaptive immune response (39 -42). In addition, increasing evidence suggests that the innate immune system is complex, and maximum activation is a result of interactions between multiple cell types (29,39,40,(42)(43)(44). Current cancer vaccines have focused on Ag-loaded mDC, but we show that optimal immunization may occur with the appropriate interplay between multiple cell types.…”

Tumor‐derived factors impaired motility and immune functions of dendritic cells through derangement of biophysical characteristics and reorganization of cytoskeleton

“…It has been generally acknowledged that there are many cytokines in the microenvironment of tumor tissues, such as TGF-b, VEGF, IL-10, gangliosides [Shurin, 2001;Peguet-Navarre, 2003] and PGE 2 [Kalinski et al, 1997], etc., that solely or cooperatively suppress the antigen presenting function of DCs, to result in immunotolerence of the tumor cells [Gabrilovich et al, 1997;Allavena et al, 1998;D'Orazio and Niederkorn, 1998;Almand et al, 2000]. The functional defects in DCs and their mechanisms caused by cancer are widely reviewed [Gabrilovich, 2004;Pinzon-Charry et al, 2005;Evel-Kabler and Chen, 2006].…”

Tumor transfected with CCL21 enhanced reactivity and apoptosis resistance of human monocyte-derived dendritic cells

“…CCL21 can promote the colocalization of naı¨ve T cells, nonpolarized memory T cells and DCs within the lymphoid node and Peyer's patch, leading to antigen presentation and T cell maturation indirectly (Campbell et al, 2001;Baekkevold et al, 2001). DCs, a sort of professional antigen-presenting cell (APC), are highly specialized in antigen uptake and presentation to T cells (Evel-Kabler and Chen, 2006). After the capture of the foreign antigen, DCs process from immature to mature state, which is demonstrated by the up-regulation of the transportation of antigen peptides and expression of co-stimulatory molecules and others, as well as release of cytokines (Tada et al, 2003;Shin et al, 2003).…”