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靶向免疫检查点:如何利用 NK 细胞对抗实体瘤

英文原题:Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors.

查看英文原题

Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors.

PubMed 2022/12/30(内容时间) Cancer Commun (Lond) Q1 · IF 28.4(JCR 2025)

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中文摘要

自然杀伤(NK)细胞是独特的先天免疫细胞,可介导抗病毒和抗肿瘤反应,因此在癌症免疫治疗中具有巨大潜力。人体 NK 细胞过继免疫治疗已显示一定疗效,但总体有限;尤其是治疗实体瘤时未能证明有效,部分原因可能是免疫抑制性肿瘤微环境(TME)降低了 NK 细胞免疫治疗效力。已知免疫检查点在形成免疫抑制性 TME、导致 NK 细胞耗竭和肿瘤免疫逃逸方面发挥重要作用。因此,要提高癌症免疫治疗效果,必须逆转 NK 细胞功能障碍并增强其效应功能。阻断免疫检查点不仅可使 NK 细胞摆脱耗竭,也能增强其强效抗肿瘤活性。本综述讨论免疫检查点阻断策略,并重点介绍嵌合抗原受体(CAR)NK 细胞如何重定向 NK 细胞靶向癌细胞,以治疗实体瘤。

展开英文摘要原文

Natural killer (NK) cells are unique innate immune cells that mediate anti-viral and anti-tumor responses.

Thus, they might hold great potential for cancer immunotherapy. NK cell adoptive immunotherapy in humans has shown modest efficacy. In particular, it has failed to demonstrate therapeutic efficiency in the treatment of solid tumors, possibly due in part to the immunosuppressive tumor microenvironment (TME), which reduces NK cell immunotherapy's efficiencies. It is known that immune checkpoints play a prominent role in creating an immunosuppressive TME, leading to NK cell exhaustion and tumor immune escape.

Therefore, NK cells must be reversed from their dysfunctional status and increased in their effector roles in order to improve the efficiency of cancer immunotherapy. Blockade of immune checkpoints can not only rescue NK cells from exhaustion but also augment their robust anti-tumor activity. In this review, we discussed immune checkpoint blockade strategies with a focus on chimeric antigen receptor (CAR)-NK cells to redirect NK cells to cancer cells in the treatment of solid tumors.

论文信息

作者
Ghaedrahmati F、Esmaeil N、Abbaspour M
第一作者单位
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.Iran
通讯作者单位
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.Iran
文献类型
综述 · 非美国政府资助研究
期刊
Cancer communications (London, England)2023 Feb
原文标识
PubMed 36585761 · DOI 10.1002/cac2.12394