Department of Nutritional Sciences, The University of Arizona, Tucson, AZ, USA.
Department of Health and Human Performance, University of Houston, Houston, TX, USA.
Clin Exp Immunol. 2018 Sep;193(3):265-274. doi: 10.1111/cei.13152.
Cytomegalovirus (CMV) infection is a potentially fatal complication in patients receiving haematopoietic stem cell transplantation (HSCT), but recent evidence indicates that CMV has strong anti-leukaemia effects due in part to shifts in the composition of natural killer (NK) cell subsets. NK cells are the primary mediators of the anti-leukaemia effect of allogeneic HSCT, and infusion of allogeneic NK cells has shown promise as a means of inducing remission and preventing relapse of several different haematological malignancies. The effectiveness of these treatments is limited, however, when tumours express human leucocyte antigen (HLA)-E, a ligand for the inhibitory receptor NKG2A, which is expressed by the vast majority of post-transplant reconstituted and ex-vivo expanded NK cells. It is possible to enhance NK cell cytotoxicity against HLA-E malignancies by increasing the proportion of NK cells expressing NKG2C (the activating receptor for HLA-E) and lacking the corresponding inhibitory receptor NKG2A. The proportion of NKG2C /NKG2A NK cells is typically low in healthy adults, but it can be increased by CMV infection or ex-vivo expansion of NK cells using HLA-E-transfected feeder cells and interleukin (IL)-15. In this review, we will discuss the role of CMV-driven NKG2C /NKG2A NK cell expansion on anti-tumour cytotoxicity and disease progression in the context of haematological malignancies, and explore the possibility of harnessing NKG2C /NKG2A NK cells for cancer immunotherapy.
巨细胞病毒 (CMV) 感染是接受造血干细胞移植 (HSCT) 的患者潜在的致命并发症，但最近的证据表明，CMV 具有强烈的抗白血病作用，部分原因是自然杀伤 (NK) 细胞亚群的组成发生了变化。NK 细胞是同种异体 HSCT 抗白血病作用的主要介导者，输注同种异体 NK 细胞已被证明是诱导缓解和预防几种不同血液恶性肿瘤复发的一种有希望的方法。然而，当肿瘤表达人类白细胞抗原 (HLA)-E 时，这些治疗的效果有限，HLA-E 是抑制性受体 NKG2A 的配体，而 NKG2A 则由移植后重建和体外扩增的 NK 细胞的绝大多数表达。通过增加表达 NKG2C（HLA-E 的激活受体）而缺乏相应抑制性受体 NKG2A 的 NK 细胞的比例，可以增强 NK 细胞对 HLA-E 恶性肿瘤的细胞毒性。在健康成年人中，NKG2C/NKG2A NK 细胞的比例通常较低，但可以通过 CMV 感染或使用 HLA-E 转染的饲养细胞和白细胞介素 (IL)-15 体外扩增 NK 细胞来增加。在这篇综述中，我们将讨论 CMV 驱动的 NKG2C/NKG2A NK 细胞扩增在血液恶性肿瘤中的抗肿瘤细胞毒性和疾病进展中的作用，并探讨利用 NKG2C/NKG2A NK 细胞进行癌症免疫治疗的可能性。
