DC at the tumor site as well as the draining lymph nodes become increasingly suppressed and contribute to T-cell anergy/deletion or to T-cell suppression via

Treg. Cancer vaccines must induce high-quality effector T cells, which as CTL or Th cells can eliminate tumor cells (including tumor-initiating cells) and/or produce advantageous cytokines. It is, however, also important to generate long-lived tumor-specific memory T cells in order to maintain anti-tumor responses as well as to prevent relapse, or as in the case of prophylactic vaccines, avoid disease. DC control Romidepsin T cells and guide their differentiation 11. The DC system is astonishingly complex and composed of different subsets with considerable plasticity 12. It is important to note that tolerance induction is the major function of DC in the steady state as also outlined in the accompanying article by Maria Rescigno 13. Only presentation of antigen by sufficiently matured DC expressing costimulatory molecules (such as membrane-bound CD86 and CD70 and/or soluble IL-12) will result in robust T-cell proliferation and differentiation, and thus effective

T-cell immunity. DC maturation is therefore a complex program; depending on both the DC subset and the type of maturation stimulus, variable Immune system set of genes and pathways are activated, leading to diverse differentiation Rucaparib concentration programs in the stimulated T cells. DC are, therefore, key to successful vaccination 14, 15. An optimal vaccine requires both antigen-targeting to DC and adequate DC maturation by adjuvants to induce a maturation program that is suitable for T-cell immunity. These crucial aspects of DC biology have until recently

been largely underestimated, while the choice/format of antigen and vaccination schedule were prioritized. In vivo DC targeting” is considered by many as the vaccine strategy of the future and will be tested in clinical trials in the coming years. In mouse models, injection of anti-DC (e.g. anti C-type lectin) antibodies fused to antigens induces tolerance by several mechanisms, but vigorous immunity can also be induced if a suitable maturation stimulus is co-delivered 16, 17. Our knowledge on the type of stimulus required in such a setting for optimal immunogenicity is expanding 18. Differential expression of receptors might allow targeting of select DC subsets and “tailor-made” immunization 19, 20. Effective immunization was also observed following delivery of TLR ligand–antigen conjugates, which contain the maturation stimulus but are not as precise in cell targeting 21.