Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

Figure 3

Ex vivo manipulation of DCs for immunotherapy. This figure schematically represents the manipulations performed with murine or human ex vivo-generated DCs for immunotherapy. DC cultures grown for about 5–10 days (left of the figure) are treated to present antigens of interest. This can be carried out by either direct peptide loading on DC cultures, as indicated by the top arrow, by genetic manipulation using viral vectors expressing the antigens of interest (central arrow), or by nonviral genetic manipulation using mRNA/DNA electroporation or transfection (bottom arrow). Any of these procedures will end up with DCs presenting the antigenic peptides in their surface associated to MHC molecules (represented as spheres labelled with a “p”). After that, the maturation stage and functional properties of the modified DCs can be manipulated by incubation with either stimulatory, as indicated by the top arrow on the right, or inhibitory stimuli, as indicated by the bottom arrow. These stimuli can be TLR agonists or antagonists, cytokines, chemokines, chemotherapy drugs, and even achieved by genetic manipulation. Pro-inflammatory DCs (DCs in orange) presenting antigenic peptides can be used for the treatment of infectious diseases and cancer, as indicated on the right by the text boxes. On the other hand, inhibitory (tolerogenic) DCs can be applied as immunosuppressive agents for the treatment of disorders and transplantation, as indicated by the text boxes.