Figure 2.

The generation of DC vaccines and the complex interplay of DC vaccines within the GBM tumor microenvironment (a): Peripherally isolated DCs or monocyte-derived DCs are pulsed with the antigen of choice with the addition of adjuvant maturation cocktails ex vivo to generate DCVs (b): DC vaccines are then administered subcutaneously or intramuscularly with the option of simultaneous injection of toxoid (Td), an adjuvant that enhances the trafficking of DC vaccines to the GBM tumor microenvironment via CCL3; (c): Primed DCs traffic to the tumor microenvironment where they must overcome the immunosuppressive effects of tumor-associated macrophages and microglia (c1) to effectively generate anti-tumor CD4+ and CD8+ T cells responses through the presentation of tumor-associated or tumor-specific antigens and expression of co-stimulatory molecules (c2). In addition to pro-tumor myeloid populations, glioma tumor cells also secrete various inhibitory molecules aimed at blunting the functionality of DCs (c3). Adjuvants targeting the tumor cells directly through mIR-326 or indirectly via NANO-DOX particles delivered by DCs have been used to enhance the anti-tumor effects of DCVs (c4).