Clinical relevance of natural killer cells following hematopoietic stem cell transplantation

Abstract

Natural killer (NK) cells are one of the first cells to recover following allogeneic hematopoietic stem cell transplantation (HSCT), and are believed to play an important role in facilitating engraftment or preventing post-transplant infection and tumor recurrence. Recent studies have provided novel insights into the mechanisms by which NK cells mediate these highly clinically relevant immunological functions. In particular, the ability of NK cells to reduce the risk of graft versus host disease (GVHD) and increase the graft versus leukemia effect (GVL) in the setting of human leukocyte antigen (HLA)-haploidentical HSCT highlights their clinical potentials. NK cells also mediate anti-viral protection, in particular against cytomegalovirus (CMV), an infection that causes significant morbidity and mortality following transplant. Another crucial function of NK cells is providing protection against bacterial infections at the mucosal barriers. NK cells achieve this by promoting anti-microbial defenses and regeneration of epithelial cells. These recent exciting findings provide a strong basis for the formulation of novel NK cell-based immunotherapies. In this review, we summarize the recent advances related to the mechanisms, functions, and future clinical prospects of NK cells that can impact post-transplant outcomes.

Keywords: Natural killer cells; immunological functions; post-transplant; stem cell.

Figure 1

Clinical relevance of donor-derived NK cells in patients following HSCT. Donor-derived bone marrow contains stems cells, immune cells including immature and mature NK cells. Mature NK cells recognize tumor cells and kill, mediate innate immune responses to prevent viral and bacterial infections, and provide help to T and B cells to coordinate the anti-tumor adoptive immune responses. Additionally, donor-derived stem cells can acquire a distinct NK phenotype by maturing in the host (patient) HLA environment. NK cells can also participate in the regeneration of tissues including the epithelial cell layers.