Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy

Figure 5

Co-stimulatory TNF ligands provide crucial signals for generation of antitumor T-cell responses. Within the antitumor T-cell immune response, CD40L-mediated CD40 costimulation of DCs by CD4+ T-helper cells is critical for the generation of CD8+ T-cell responses. 4-1BBL expressed on DCs stimulates the generation of T-cell response, while at the same time inhibiting the formation of inducible regulatory T-cells in the tumor micro-environment. CD70 serves to efficiently prime CD4+ and CD8+ T cell responses, to enhance T-cell survival, and to optimize effector function. OX40 is transiently upregulated upon T-cell activation and enhances clonal expansion, survival, proinflammatory cytokine production, and generation of memory CD4 T-cells and enhances CD8+ T-cell survival and expansion.