The role of γδ T cells in the context of allogeneic stem cell transplantation

Allogeneic stem cell transplantation is currently the only curative approach for a variety of malignant and non-malignant diseases. In the early transplant era, the intent of this treatment was to apply an intensive myeloablative regimen to eliminate residual malignant cells followed by the hematopoietic rescue of the patients with donor hematopoietic stem cells. However, the focus has shifted over time and allogeneic transplantation is nowadays seen as a cellular therapy in which the donor-derived immune system mounts an anti-infectious and especially an anti-tumor effect in the posttransplant phase. In order to further augment the anti-tumor effect, various approaches have been developed, including the manipulation of the donor-derived immune system in vivo or the adoptive transfer of ex vivo-expanded donor-derived effector cells. Based on their lack of alloreactivity, γδ+ T cells are shifting into the spotlight of research in the context of allogeneic transplantation. Their exploitation with regard to their anti-infectious and anti-tumor properties and their in vivo and ex vivo manipulation will lead to new therapeutic approaches to improve the outcome of patients after allogeneic stem cell transplantation. In this review, the important role of γδ+ T cells in allogeneic matched and mismatched transplantation is summarized and an outlook is discussed on how to best make use of this unique cell population.