Insights and strategies to promote immune tolerance in allogeneic hematopoietic stem cell transplantation recipients

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best immunotherapeutic strategy to treat hematological malignancies. The alloreactive donor T cells in the graft eliminate tumor cells and promote engraftment and immune reconstitution. However, these T cells are also involved in mediating graft-vs-host disease (GVHD), which contributes to higher morbidity and mortality in allo-HSCT patients. Global immunosuppressive agents are primary therapeutic options to treat GVHD, but their usage often leads to undesirable side effects such as tumor relapse, opportunistic infections, and organ toxicity. Hence, balancing graft-vs-leukemia and GVHD influences the outcome of allo-HSCT. Strategies promoting immune tolerance in allo-HSCT could maintain immune balance and also avoid the usage of immunosuppressants. In this chapter, we discuss the pathophysiology of GVHD and recent strategies in promoting immune tolerance in allo-HSCT.