Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Front Immunol. 2019 Aug 9;10:1782. doi: 10.3389/fimmu.2019.01782. eCollection 2019.
Ovarian cancer (OC) is diagnosed in ~22,000 women in the US each year and kills 14,000 of them. Often, patients are not diagnosed until the later stages of disease, when treatment options are limited, highlighting the urgent need for new and improved therapies for precise cancer control. An individual's immune function and interaction with tumor cells can be prognostic of the response to cancer treatment. Current emerging therapies for OC include immunotherapies, which use antibodies or drive T cell-mediated cancer recognition and elimination. In OC, these have been limited by adverse side effects and tumor characteristics including inter- and intra-tumoral heterogeneity, lack of targetable antigens, loss of tumor human leukocyte antigen expression, high levels of immunosuppressive factors, and insufficient immune cell trafficking. Natural killer (NK) cells may be ideal as primary or collateral effectors to these nascent immunotherapies. NK cells exhibit multiple functions that combat immune escape and tumor relapse: they kill targets and elicit inflammation through antigen-independent pathways and detect loss of HLA as a signal for activation. NK cells are efficient mediators of tumor immune surveillance and control, suppressed by the tumor microenvironment and rescued by immune checkpoint blockade. NK cells are regulated by a variety of activating and inhibitory receptors and already known to be central effectors across an array of existing therapies. In this article, we highlight interactions between NK cells and OC and their potential to change the immunosuppressive tumor microenvironment and participate in durable immune control of OC.
卵巢癌（OC）在美国每年诊断出约 22000 名女性，其中 14000 人因此死亡。通常，患者在疾病晚期才被诊断出来，此时治疗选择有限，这突显了迫切需要新的和改进的疗法来精确控制癌症。个体的免疫功能和与肿瘤细胞的相互作用可以预测对癌症治疗的反应。目前用于 OC 的新兴疗法包括免疫疗法，其使用抗体或驱动 T 细胞介导的癌症识别和消除。在 OC 中，这些疗法受到不良反应和肿瘤特征的限制，包括肿瘤内和肿瘤间异质性、缺乏可靶向的抗原、肿瘤人类白细胞抗原表达丧失、高水平的免疫抑制因子以及免疫细胞迁移不足。自然杀伤 (NK) 细胞可能是这些新兴免疫疗法的理想主要或辅助效应细胞。NK 细胞具有多种功能，可以对抗免疫逃逸和肿瘤复发：它们通过非抗原依赖性途径杀死靶细胞并引发炎症，并检测 HLA 的丧失作为激活信号。NK 细胞是肿瘤免疫监测和控制的有效介质，被肿瘤微环境抑制，并被免疫检查点阻断剂挽救。NK 细胞受多种激活和抑制受体的调节，并且已经被认为是多种现有疗法的核心效应细胞。在本文中，我们强调了 NK 细胞与 OC 之间的相互作用及其改变免疫抑制肿瘤微环境和参与 OC 持久免疫控制的潜力。
