文章：

NK细胞和癌症：你可以教先天细胞新的技巧

NK cells and cancer: you can teach innate cells new tricks

原文发布日期：2015-12-18

DOI: 10.1038/nrc.2015.5

类型: Review Article

开放获取: 否

要点：

1. Natural killer (NK) cells have a primordial role in tumour immunosurveillance. Given their potent antitumour activity, therapeutic manipulation of NK cells provides an attractive strategy for cancer treatment.
2. A balance of inhibitory and stimulatory signals delivered by numerous receptors regulates NK cell functions (cytotoxicity, cytokine production and proliferation). NKG2D is the best characterized of these activating receptors and is directly involved in the recognition of tumours that express NKG2D ligands.
3. NK cells detect and eliminate tumour cells that are deficient in major histocompatibility complex (MHC) class I molecules (missing self), have upregulated stress ligands that are recognized by activating NK cell receptors (induced self), or are coated with antibodies specific for tumour antigens, enabling recognition by NK cells expressing the CD16 Fc receptor, which triggers antibody-dependent cell-mediated cytotoxicity.
4. Immunoediting of tumour cells by NK cells leads to tumour variants that can evade NK cell-mediated responses. Direct and indirect tumour escape mechanisms include secretion of immunosuppressive factors, shedding of ligands for the activating NK cell receptors and induction of ligands for activating NK cell receptors on healthy cells that can serve as decoys.
5. Current checkpoint blockade agents used to activate T cells in cancer patients, such as antibodies against PD1, may also target NK cells. Checkpoint blockade targeting inhibitory receptors shared by NK cells and T cells are currently under clinical evaluation.
6. In addition to engineered T cells, NK cells and their receptors represent an attractive alternative for the use of chimeric antigen receptors.
7. Immunotherapeutic approaches such as the generation of bispecific linkers that engage activating NK cell receptors and tumour-specific antigens are also being developed to unleash the antitumour potential of NK cells.

要点翻译：

1. 自然杀伤（NK）细胞在肿瘤免疫监视中具有原始作用。鉴于其强大的抗肿瘤活性，对NK细胞进行治疗性操控为癌症治疗提供了有吸引力的策略。
2. 由众多受体传递的抑制性和刺激性信号的平衡调控着NK细胞功能（细胞毒性、细胞因子产生和增殖）。NKG2D是这些激活受体中特征最明确的，直接参与识别表达NKG2D配体的肿瘤。
3. NK细胞检测并清除主要组织相容性复合体（MHC）I类分子缺陷（缺失自我）、上调应激配体被NK细胞激活受体识别（诱导自我），或被肿瘤抗原特异性抗体包被的肿瘤细胞，后者使得表达CD16 Fc受体的NK细胞能够识别，从而触发抗体依赖性细胞介导的细胞毒性。
4. NK细胞对肿瘤细胞的免疫编辑导致产生能够逃避NK细胞介导反应的肿瘤变异体。直接和间接的肿瘤逃逸机制包括分泌免疫抑制因子、脱落激活NK细胞受体的配体，以及在健康细胞上诱导激活NK细胞受体的配体作为诱饵。
5. 目前用于激活癌症患者T细胞的检查点阻断剂，如抗PD1抗体，也可能靶向NK细胞。针对NK细胞和T细胞共享的抑制性受体的检查点阻断目前正在进行临床评估。
6. 除了工程化T细胞外，NK细胞及其受体为使用嵌合抗原受体提供了一个有吸引力的替代方案。
7. 诸如开发能够结合激活NK细胞受体和肿瘤特异性抗原的双特异性连接分子等免疫治疗方法也正在研发中，以释放NK细胞的抗肿瘤潜力。

英文摘要：

Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer.

摘要翻译： 

自然杀伤（NK）细胞是原型的先天淋巴样细胞，具有强大的细胞溶解功能，可抵御微生物感染和肿瘤。在此，我们回顾了NK细胞在癌症免疫监视中的作用证据，并强调了在治疗癌症中靶向NK细胞的新治疗方法。

原文链接：

NK cells and cancer: you can teach innate cells new tricks