The influence of mTOR inhibitors on immunity and the relationship to post-transplant malignancy

The known role of mammalian target of rapamycin (mTOR) in the immune response has been rapidly evolving, from what was once thought to be a simple immunosuppressive antiproliferative effect on T cells to a very complex central role that serves to integrate multiple signals given to T cells, B cells and antigen-presenting cells. The complexity of this topic is demonstrated by recent data suggesting that mTOR inhibition can either inhibit or promote certain aspects of immune responses, depending on the nature of the antigenic stimulus, and the environmental conditions cueing the cellular immunological players. There is even evidence that, under mTOR inhibition, an immune response to one foreign entity (for example, an organ transplant) may be simultaneously completely different to that of another (for example, tumour or microorganism). To understand how this might be possible, it is necessary to investigate the central role that mTOR seems to have in shaping the immune response. This review is aimed at examining how mTOR controls the development and function of key immune cells, and puts this information primarily in the context of organ transplant rejection and post-transplant malignancy.