Gotthardt Dagmar, Sexl Veronika
Department for Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine , Vienna , Austria.
Front Immunol. 2017 Jan 18;7:694. doi: 10.3389/fimmu.2016.00694. eCollection 2016.
Natural killer (NK)-cells are major players in the fight against viral infections and transformed cells, but there is increasing evidence attributing a disease-promoting role to NK-cells. Cytokines present in the tumor microenvironment shape NK-cell maturation, function, and effector responses. Many cytokines signal the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway that is also frequently altered and constitutively active in a broad range of tumor cells. As a consequence, there are currently major efforts to develop therapeutic strategies to target this pathway. Therefore, it is of utmost importance to understand the role and contributions of JAK-STAT molecules in NK-cell biology-only this knowledge will allow us to predict effects of JAK-STAT inhibition for NK-cell functions and to successfully apply precision medicine. We will review the current knowledge on the role of JAK-STAT signaling for NK-cell functions and discuss conditions involved in the switch from NK-cell tumor surveillance to disease promotion.
自然杀伤（NK）细胞是对抗病毒感染和转化细胞的主要参与者，但越来越多的证据表明NK细胞具有促进疾病的作用。肿瘤微环境中存在的细胞因子塑造了NK细胞的成熟、功能和效应反应。许多细胞因子通过Janus激酶（JAK）-信号转导子和转录激活子（STAT）途径发出信号，该途径在广泛的肿瘤细胞中也经常发生改变并持续激活。因此，目前人们正在大力开发针对该途径的治疗策略。因此，了解JAK-STAT分子在NK细胞生物学中的作用和贡献至关重要——只有这些知识才能让我们预测JAK-STAT抑制对NK细胞功能的影响，并成功应用精准医学。我们将综述目前关于JAK-STAT信号传导对NK细胞功能作用的知识，并讨论从NK细胞肿瘤监测转变为促进疾病的相关条件。
