We are most grateful to the patients and controls who generously donated blood samples and to Dr Misbah, Dr Lorton and Dr Patel, who care for these patients. We are also grateful to the staff at the Department of Clinical Laboratory Immunology at the Churchill Hospital, Oxford for their support and performing the lymphocyte subset analyses. Authors’ conflicts of interest: None declared. “
“Natural killer (NK) cell adoptive

transfer is a promising approach for cancer immunotherapy; however, its PF-562271 development has been hindered by the lack of efficient methods to produce large numbers of functional NK cells. In this study, we engineered the leukaemia cell line K562 to express FG-4592 concentration CD137 ligand (CD137L) and membrane-bound interleukin (mbIL)-21 on the cell surface, and used these cells to expand NK cells from the peripheral blood mononuclear cells. We found that purity of the NK cells (CD3−CD56+/CD16+) increased from less than 30% to above 95% after a 3-week expansion and proliferation of the cells was sustained for more than 8 weeks. The surface expression

of NK cell activating and inhibitory receptors, except for NKp80, was clearly increased with the expansion, and NK cell-mediated killing activity was also enhanced significantly. However, these changes in both phenotype and function were clearly reversed by JSI-124, a specific signal Forskolin transducer and activator of transcription-3 (STAT-3) inhibitor. Taken together, data showed that the combination of mbIL-21 and CD137L could efficiently induce the formation of functional human NK cells from peripheral blood mononuclear cells, and STAT-3 inhibition could impair this induction. Therefore, STAT-3 activation may benefit human NK cell proliferation and cytotoxicity, and provide valuable clinical applications in NK cell immunotherapy against viral infectious diseases and cancers.

Human natural killer (NK) cells are a subset of peripheral blood lymphocytes that are defined by their expression of CD56 and/or CD16 and the absence of T cell receptor CD3 [1]. NK cells can recognize and subsequently kill virus-infected and transformed cells in the absence of prior stimulation, and play a critical role in the immune surveillance of virus infectious diseases and cancers. NK cell killing is regulated through balanced signals from the activating and inhibitory receptors on NK cell surface [2]. A large number of studies have demonstrated that NK cells could elicit strong anti-tumour efficacy, and are promising effectors for adoptive immunotherapy against cancers [3]. NK cell alloreactivity could control leukaemia relapse without causing graft-versus-host disease (GVHD) [4]. Adoptive transfer of NK cells has been tested in early-phase clinical trials and has emerged as a safe and potentially efficacious immunotherapy for cancers [5].