Dendritic cell-based vaccine efficacy: aiming for hot spots

Abstract

Many approaches for cancer immunotherapy have targeted dendritic cells (DCs), directly or indirectly, for the induction of antitumor immune responses. DC-based vaccines have been developed using a wide variety of ex vivo DC culture conditions, antigen (Ag) source and loading strategies, maturation agents, and routes of vaccination. Adjuvants are used to activate innate immune cells at the vaccine injection site, to promote Ag transport to the draining lymph nodes (LNs) and to model adaptive immune responses. Despite years of effort, the effective induction of strong and durable antitumor T-cell responses in vaccinated patients remains a challenge. The study of vaccine interactions with other immune cells in the LNs and, more recently, in the injection site has opened new doors for understanding antitumor effector T-cell licensing and function. In this review, we will briefly discuss the relevant sites and up-to-date facts regarding possible targets for antitumor vaccine refinement. We will focus on the processes taking place at the injection site, adjuvant combinations and their role in DC-based vaccines, LN homing, and modeling vaccine-induced immune responses capable of controlling tumor growth and generating immune memory.

Keywords: antitumor T cells; cancer vaccines; dendritic cells; draining lymph nodes; immunotherapy; vaccine injection site.

Figure 1

“Hot spots” in DC-based vaccine design. Current approaches for cancer immunotherapy targeting DC include multiple steps, resulting in one out of hundreds of possible combinations, with different antitumor immune responses. Direct or indirect strategies can be achieved either ex vivo or in vivo, with particular implications to be considered in each case. We identify the relevant sites, or “hot spots,” that become targets for antitumor vaccine refinement according to recent years of basic and clinical investigation. First, the skin as an injection site can be widely activated in order to improve vaccine efficacy. Second, DC-based vaccine migration to the lymph node compartment can be exploited to enhance the induction of Ag-specific immune effectors. Finally, systemic vaccine-induced immune response should overcome local immunosuppression to control tumor growth and to generate long-term immune memory.