Article Figures & Data
Figures
- FIGURE 1.
Functional plasticity of DCs: subsets. Human LCs induce potent CTL responses, possibly via IL-15. At least four lines of evidence indicate that human LCs are remarkable at inducing CTL responses ex vivo: 1) LCs loaded with a MHC class I peptide potently induce the proliferation of peptide-specific naive CD8+ T cells; 2) LCs expand naive CD8+ T cells with high avidity against peptide/MHC class I complex; 3) naive CD8+ T cells primed by LCs express high levels of cytotoxic molecules, such as granzymes A, B, and perforin, and display a high cytotoxicity; and 4) LCs are efficient at cross-presentation of Ags. Human CD14+ dermal DCs induce potent humoral responses via IL-12. When DCs form the complex with T cells and B cells at extrafollicular sites, IL-12 derived from activated DCs promotes B cells to differentiate into Ab-secreting cells by two different paths: a direct path via DC–B interaction, and an indirect path through induction of IL-21–producing T follicular helper-like cells. Thus, the most efficient CD8+ T cell vaccines might be those that build on DCs expressing the molecular signatures of LCs, for example, IL-15 DCs.
- FIGURE 2.
Functional plasticity of DCs: maturation signals. DCs exist in distinct functional states, resting and activated, or immature and mature. Depending on the signal, DCs will undergo activation/maturation, the quality of which will determine the type of elicited adaptive immunity.
- FIGURE 3.
DC vaccines in combination therapies. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current approaches is limited, possibly because tumors invade the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells, and Tregs. To improve the clinical efficacy of immunotherapies, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs, and allow the breakdown of an immunosuppressive tumor microenvironment. This can be achieved by developing combination therapies targeting these three major components.
- FIGURE 4.
Approaches to DC-based immune intervention in cancer. 1) Vaccines based on Ag with or without adjuvant that targets DCs randomly. That might result in vaccine Ags being taken up by a “wrong” type of DCs in the periphery, which might lead to “unwanted” type of immune response. Vaccine Ags could also flow to draining lymph nodes, where they can be captured by resident DCs. 2) Vaccines based on ex vivo generated tumor Ag-loaded “artificial” DCs that are injected back into patients. 3) Specific in vivo DC targeting with anti-DC Abs fused with Ags and with DC activators. 4) Next generation clinical trials will test optimized DC vaccines combined with patient-adjusted approaches to block Tregs and to break down the tumor environment. These therapies will be tested in preselected patients, thereby leading to personalized therapy.
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