Cancer immunotherapy via dendritic cells

Abstract

The molecular identification of human cancer antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Cancer vaccines aim to induce tumour-specific effector T cells that can reduce the tumour mass and to induce tumour-specific memory T cells that can control tumour relapse. Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural targets for antigen delivery. DCs provide an essential link between the innate and the adaptive immune responses. DCs are at the centre of the immune system owing to their ability to control both tolerance and immune responses. These key properties of DCs render them the central candidates for antigen delivery and vaccination, including therapeutic vaccination against cancer. The immune system has the potential to eliminate neoplastic cells. However, tumour cells alone are poor antigen-presenting cells (APCs). Studies with mouse models demonstrate that the generation of protective anti-tumour immune responses depends on the presentation of tumour antigens by DCs. When compared with other APCs, such as macrophages, DCs are extremely efficient at antigen presentation and inducing T cell immunity, thus explaining their nickname of 'professional APCs'. Mice and humans have distinct functional subsets of DCs that generate different types of immune response. DCs are also able to mature; that is, to acquire novel functions following microbe encounters. Under steady state conditions, DCs in peripheral tissues are 'immature'. These immature DCs induce tolerance either through T cell deletion or through inducing the expansion of regulatory and/or suppressor T cells. DCs promptly respond to environmental signals and differentiate into mature DCs that can efficiently launch immune responses. It is now accepted that the adjuvant component of vaccines primarily acts by triggering DC maturation. DCs are important targets for therapeutic interventions in cancer. Two themes of research are growing: first, how cancer cells alter DC physiology; and second, how we can build on the powerful properties of DCs to generate novel cancer immunotherapies (including vaccines).