Harnessing dendritic cells to generate cancer vaccines

Passive immunotherapy of cancer (i.e., transfer of T cells or antibodies) can lead to some objective clinical responses, thus demonstrating that the immune system can reject tumors. However, passive immunotherapy is not expected to yield memory T cells that might control tumor outgrowth. Active immunotherapy with dendritic cell (DC) vaccines has the potential to induce tumor-specific effector and memory T cells. Clinical trials testing first-generation DC vaccines pulsed with tumor antigens provided a proof-of-principle that therapeutic immunity can be elicited. Newer generation DC vaccines are built on the increased knowledge of the DC system, including the existence of distinct DC subsets and their plasticity all leading to the generation of distinct types of immunity. Rather than the quantity of IFN-γ-secreting CD8⁺ T cells, we should aim at generating high-quality, high-avidity, polyfunctional effector CD8⁺ T cells able to reject tumors and long-lived memory CD8⁺ T cells able to prevent relapse.