29 mars 2012 4 29 /03 /mars /2012 07:12
The tumour microenvironment is an important aspect of cancer biology that contributes to tumour initiation, tumour progression and responses to therapy. Cells and molecules of the immune system are a fundamental component of the tumour microenvironment. Importantly, therapeutic strategies can harness the immune system to specifically target tumour cells and this is particularly appealing owing to the possibility of inducing tumour-specific immunological memory, which might cause long-lasting regression and prevent relapse in cancer patients. The composition and characteristics of the tumour microenvironment vary widely and are important in determining the anti-tumour immune response. For example, certain cells of the immune system, including natural killer cells, dendritic cells (DCs) and effector T cells, are capable of driving potent anti-tumour responses. However, tumour cells often induce an immunosuppressive microenvironment, which favours the development of immunosuppressive populations of immune cells, such as myeloid-derived suppressor cells and regulatory T cells. Understanding the complexity of immunomodulation by tumours is important for the development of immunotherapy. Various strategies are being developed to enhance anti-tumour immune responses, including DC-based vaccines and antagonists of inhibitory signalling pathways to overcome 'immune checkpoints'. Existing therapies are also being investigated for their ability to induce an anti-tumour immune response, which could lead to the administration of combination immunotherapies that provide a more efficacious and enduring response. However, there are issues that remain to be understood. In particular, it is clear that there is variability in the ability of a tumour to induce an immune response and hence there is debate about the determinants of tumour immunogenicity. It will be important to resolve these issues in order to predict or modulate responses to immunotherapies. The articles in this specially commissioned Focus on Tumour immunology & immunotherapy from Nature Reviews Cancer and Nature Reviews Immunology, together with some recent Research Highlights, describe our progress in understanding the complexity of the immune system in cancer biology and the promise of immunotherapy.