The rising role of natural killer cells in patients with malignant hematological disorders and in recipients of hematopoietic stem cell transplantation

Abstract

Natural killer (NK) cells, the third population of lymphoid cells, comprise 5%-25% of peripheral blood (PB) lymphocytes and represent the irst line of defense against infections and tumors [1-7]. They can be derived from: bone marrow, PB, cryopreserved umbilical cord blood (UCB), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and various cell lines such as NK-92 and KHYG-1 [1]. NK cells; which have been divided into cytotoxic, tolerant, and regulatory subsets; are classi ied into: (1) naïve CD56 bright CD 16 dim CD 3 dim cells, (2) mature CD56 dim CD16 bright CD3 dim cells, and (3) lymphoid tissue-resident CD69+/CXCR6+ NK cells [1,2,8-11]. Although NK cells have been traditionally considered as part of the innate immune system, they have recently been shown to exhibit many of the features associated with adaptive immunity [8,12]. The functions of NK cells which are in luenced by several cytokines include: elimination of infected cells, destruction of cancer cells, reducing the incidence of graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), and regulation of pregnancy outcome [10,11,13]. NK cell function is inely tuned by activating and inhibitory receptors that recognize both foreign and self-antigens expressed by NK cell-susceptible targets [7,14]. Activated NK cells interact with dendritic cells (DCs) and mesenchymal stem cells (MSCs) and the complicated crosstalks between NK cells, MSCs, and DCs may alter the functions of any of the 3 cell types [15-27].