Natural Killer Cells in Post-Transplant Lymphoproliferative Disorders

SIMPLE SUMMARY: Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications. The clinical and pathological spectrum of PTLD is broad; however, most cases of PTLD are associated with Epstein–Barr virus (EBV) infection and the use of immunosuppression treatment required to prevent graft rejection. While T-cell impairment is known to play a critical role in the immunopathogenesis of EBV complications post-transplantation, the role of natural killer (NK) cells remains more elusive. NK cells are key elements of the innate immune system that use a sophisticated array of activating, costimulatory, and inhibitory receptors to kill virally infected and/or cancerous cells. In this review we highlight the role of NK cells in the pathogenesis of PTLD, and also identify future avenues for NK cell therapy research. ABSTRACT: Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications arising after solid organ or hematopoietic stem cell transplantations. Although the majority of these lymphoproliferations are of B cell origin, and are frequently associated with primary Epstein–Barr virus (EBV) infection or reactivation in the post-transplant period, rare cases of T cell and natural killer (NK) cell-originated PTLDs have also been described. A general assumption is that PTLDs result from the impairment of anti-viral and anti-tumoral immunosurveillance due to the long-term use of immunosuppressants in transplant recipients. T cell impairment is known to play a critical role in the immune-pathogenesis of post-transplant EBV-linked complications, while the role of NK cells has been less investigated, and is probably different between EBV-positive and EBV-negative PTLDs. As a part of the innate immune response, NK cells are critical for protecting hosts during the early response to virus-induced tumors. The complexity of their function is modulated by a myriad of activating and inhibitory receptors expressed on cell surfaces. This review outlines our current understanding of NK cells in the pathogenesis of PTLD, and discusses their potential implications for current PTLD therapies and novel NK cell-based therapies for the containment of these disorders.