Emerging role of Natural killer cells in oncolytic virotherapy.
Emerging role of Natural killer cells in oncolytic virotherapy.
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DOI：
10.2147/itt.s55549
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发表时间：
2015
影响因子：
7.2
通讯作者：
Rommelaere J
中科院分区：
文献类型：
--
作者：
Bhat R;Rommelaere J
自然杀伤（NK）细胞是淋巴细胞的一种亚型，可启动针对肿瘤和病毒感染细胞的先天免疫反应。NK细胞杀死靶细胞或产生细胞因子的能力取决于激活和抑制细胞表面受体信号之间的平衡。NK细胞的治疗包括激活内源性NK细胞和/或通过造血干细胞移植/过继细胞治疗进行外源性转移。为了利用NK细胞的多种功能能力进行癌症免疫治疗，了解NK细胞生物学及其潜在的调节机制是很重要的。恶性肿瘤中普遍存在的免疫抑制状态产生了对创新疗法的需求。溶瘤病毒是一种新型的抗癌药物，对肿瘤细胞具有选择性趋向性，对人体缺乏致病性，但使用溶瘤病毒治疗（OVT）面临多重挑战。越来越多的证据表明，宿主免疫反应可能严重影响OVT的结果。传统上，免疫系统被认为是通过先天免疫效应物介导的病毒清除或通过消除感染细胞的适应性抗病毒免疫反应来限制治疗效果的。在OVT中确实需要设计有效的策略来规避NK细胞的早期抗病毒活性，并增强NK细胞介导的晚期抗肿瘤反应。溶瘤病毒固有的免疫刺激能力及其表达异源免疫刺激分子（如细胞因子）的可能性支持使用这些药物除了诱导直接的溶瘤作用外，还可以增强抗肿瘤免疫反应。OVT确实在各种临床试验中显示出有希望的治疗效果。在这里，我们回顾了NK细胞的生物学，涉及NK细胞实现癌症治疗的策略，特别是NK细胞在OVT中的新作用。
Natural killer (NK) cells constitute a subtype of lymphocytes that initiate innate immune responses against tumors and virus-infected cells. The ability of NK cells to kill target cells or to produce cytokines depends on the balance between signals from activating and inhibitory cell-surface receptors. Therapies with NK cells involve activation of endogenous NK cells and/or exogenous transfer by hematopoietic stem cell transplantation/adoptive cell therapy. To exploit the diverse functional abilities of NK cells for cancer immunotherapy, it is important to understand NK cell biology and the underlying regulatory mechanisms. The state of immune suppression prevalent in malignancies creates the need for innovative therapies. Oncolytic viruses are novel anticancer agents showing selective tropism for tumor cells and lacking pathogenicity in humans, but the use of oncolytic virotherapy (OVT) presents multiple challenges. An increasing body of evidence suggests that the host immune response may critically influence the outcome of OVT. Classically, the immune system is thought to limit the efficacy of therapy through virus clearance mediated by innate immune effectors or through adaptive antiviral immune responses eliminating infected cells. Effective strategies do need to be designed in OVT to circumvent the early antiviral activity of NK cells and to augment late NK-cell-mediated antitumor responses. The intrinsic immunostimulating capacity of oncolytic viruses and the possibility of engineering them to express heterologous immunostimulatory molecules (eg, cytokines) support the use of these agents to enhance antitumor immune responses besides inducing direct oncolytic effects. OVT has indeed shown promising therapeutic outcomes in various clinical trials. Here, we review the biology of NK cells, strategies involving NK cells for achieving cancer therapy, and, more particularly, the emerging role of NK cells in OVT.