New frontiers in immunosuppression

Immunosuppressive therapy is arguably the most important component of medical care after lung transplantation. The goal of immunosuppression is to prevent acute and chronic rejection while maximizing patient survival and long-term allograft function. However, the benefits of immunosuppressive therapy must be balanced against the side effects and major toxicities of these medications. Immunosuppressive agents can be classified as induction agents, maintenance therapies, treatments for acute rejection and chronic rejection and antibody directed therapies. Although induction therapy remains an area of controversy in lung transplantation, it is still used in the majority of transplant centers. On the other hand, maintenance immunosuppression is less contentious; but, unfortunately, since the creation of three-drug combination therapy, including a glucocorticoid, calcineurin inhibitor and anti-metabolite, there have been relatively modest improvements in chronic maintenance immunosuppressive regimens. The presence of HLA antibodies in transplant candidates and development of de novo antibodies after transplantation remain a major therapeutic challenge before and after lung transplantation. In this chapter we review the medications used for induction and maintenance immunosuppression along with their efficacy and side effect profiles. We also review strategies and evidence for HLA desensitization prior to lung transplantation and management of de novo antibody formation after transplant. Finally, we review immune tolerance and the future of lung transplantation to limit the toxicities of conventional immunosuppressive therapy.