Harnessing allogeneic NK cells: improving outcomes with tailored donor lymphocyte infusion

Since researchers first began to uncover the mechanisms underlying allogeneic transplantation, the focus has been on T cells. T cells are a major instigator of graft-versus-host disease (GVHD). The clear association between GVHD occurrence and subsequent reduction in relapse supported concentrating on T cells as the masterminds behind graft-versus-tumor (GVT) effects. Recently, an alternative mediator of GVT has taken center stage: natural killer (NK) cells. Part of the appeal of NK cells is their potential to provide antitumor immunity without GVHD. Donor lymphocyte infusion has been the predominant treatment of relapse after allogeneic transplant, but the mix of lymphocytes includes CD8+ T cells and, consequently, a substantial risk for GVHD. In this issue of the JCI, Shapiro and colleagues developed an adoptive NK cell transfer platform to treat relapse after haploidentical allogeneic transplant. The study demonstrated safety, sought to determine resistance mechanisms, and provided avenues for future research.