Cellular-Based Immunotherapies for Patients with Glioblastoma Multiforme

Figure 1

DC-based active immunotherapy for GBM. DCs display a unique capacity to induce and to maintain T-cell responses. Mature DCs are generated from PBMC in vitro in the presence of IL-4, GM-CSF, TNF-alpha, IL-1beta, PGE2, IFN-gamma, and other cytokines, in addition to TLR agonists. Subsequently, they are loaded with GBM or glioblastoma stem cell lysates, GBM-associated antigen-derived peptides, protein, or RNA. Due to their high surface expression of HLA-peptide-complexes and costimulatory molecules, DCs could efficiently activate and expand CD8⁺ CTLs and CD4⁺ Th cells. CD8⁺ CTLs are able to recognize and eliminate tumor cells, especially the GBM stem cells (CD133). CD4⁺ Th cells enhance the capacity of DCs to induce CTLs by the interaction between CD40 on DCs and CD40 ligand on activated CD4⁺ T cells. In addition, CD4⁺ T cells help in the maintenance and expansion of CTLs by secreting IL-2. CTLs: cytotoxic T cells; imDC: immature dendritic cells; GZMB: granzyme B; GSCs: glioblastoma stem cells, HLA: human leukocyte antigen; IL: interleukin; IFN: interferon; mDC: mature dendritic cells; PBMC: peripheral blood mononuclear cells; TCR: T-cell receptor; Th: T helper cell; TLR: toll-like receptor.