Knowledge-based immune-therapeutic advances for transplantation and cancer.

Increased knowledge about immune responses to what is perceived as 'foreign' or 'non-self' has revealed extraordinary levels of complexity. Research uncovering these has the potential to optimise immunotherapy. Remarkable progress has been made in transplantation leading to much less acute rejection and a very significant increase in long-term survival. These and other beneficial results have been achieved by stepwise advances, using combinations of less toxic chemotherapies with biological immunosuppressive agents alongside innovatory surgical skills. However, rejection is the default pathway for entities deemed 'foreign', including mistaken suspects like autoantigens. For tumour immunotherapy the identification of bona fide tumour antigens recognised by B and/or T cell receptors has mushroomed but has yet to be optimised to take into account mutations leading to tumour evasion. We are now at the beginning of a road that looks more hopeful by being informed of the complexities. Basic and translational research between the late 1960s and now have yielded an extraordinarily rich harvest of new knowledge. More is to come, further insight is needed and new paradigms explored.