Does our current understanding of immune tolerance, autoimmunity, and immunosuppressive mechanisms facilitate the design of efficient cancer vaccines?

The therapeutic use of the immune system to attack cancer cells has been a longstanding vision among tumour immunologists. However, most human tumours are poorly immunogenic and are able to invade the host immune system. Although these obstacles are clearly critical to cancer vaccine development, the induction of a strong anti-tumour immune response may rely on the activation of high affinity T cells through a molecular mimicry mechanism which involves cross-reactive recognition of foreign antigens mimicking the structure of tumour proteins. Taking into account the disparity in HLA molecules needed to present shared antigens; in late 1990s Stauss et al. described the possibility of generating allorestricted high affinity cytotoxic T cells against synthetic self-peptides bound to non-self-MHC molecules. In addition to the strategies indicated above, the inhibition of the immunosuppressive mechanisms associated with tumour invasion of the immune system using RNA interference also offers a new approach to vaccine design. This review highlights the problem of immune tolerance, the induction of autoreactive T cells, and describes strategies to enhance tumour immunity.