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抗肿瘤与健康组织保护中的 NK 细胞受体:机制与治疗进展

英文原题:NK cell receptors in anti-tumor and healthy tissue protection: Mechanisms and therapeutic advances.

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NK cell receptors in anti-tumor and healthy tissue protection: Mechanisms and therapeutic advances.

PubMed 2024/09/18(内容时间) Immunol Lett Q3 · IF 3.2(JCR 2025)

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中文摘要

自然杀伤(NK)细胞是固有免疫系统的重要组成部分,以其无需抗原呈递即可靶向并消灭癌细胞且不损伤正常组织的能力而著称。由于其具有多种调节细胞毒活性的激活性和抑制性受体,这些细胞在肿瘤免疫监视中至关重要。

然而,肿瘤微环境可通过多种机制抑制NK细胞功能。近几十年来,研究集中于克服这些肿瘤逃逸机制。最初,研究重点放在增强T细胞活性上,旨在增强T细胞反应的免疫治疗方法取得了令人瞩目的成果。

然而,相当数量的患者未能从这些治疗中获益,仍在寻求有效的替代方案。在此背景下,鉴于NK细胞强大的细胞毒能力、安全性特征以及对T细胞耐药肿瘤(如缺乏HLA-I表达的肿瘤)的活性,NK细胞为开发新疗法提供了有前景的途径。近期免疫治疗进展包括通过免疫检查点抑制剂、细胞因子、过继性NK细胞治疗和CAR-NK细胞技术来恢复和增强NK细胞活性的策略。本综述全面概述了NK细胞受体、阻碍NK细胞功能的肿瘤逃逸机制以及基于NK细胞的肿瘤免疫治疗的不断发展领域,重点介绍了为开发更有效和更有针对性的肿瘤治疗策略所做的持续努力。

展开英文摘要原文

Natural Killer (NK) cells are integral to the innate immune system, renowned for their ability to target and eliminate cancer cells without the need for antigen presentation, sparing normal tissues. These cells are crucial in cancer immunosurveillance due to their diverse array of activating and inhibitory receptors that modulate their cytotoxic activity.

However, the tumor microenvironment can suppress NK cell function through various mechanisms. Over recent decades, research has focused on overcoming these tumor escape mechanisms. Initially, efforts concentrated on enhancing T cell activity, leading to impressive results with immunotherapeutic approaches aimed at boosting T cell responses. Nevertheless, a substantial number of patients do not benefit from these treatments and continue to seek effective alternatives. In this context, NK cells present a promising avenue for developing new treatments, given their potent cytotoxic capabilities, safety profile, and activity against T cell-resistant tumors, such as those lacking HLA-I expression.

Recent advancements in immunotherapy include strategies to restore and amplify NK cell activity through immune checkpoint inhibitors, cytokines, adoptive NK cell therapy, and CAR-NK cell technology. This review provides a comprehensive overview of NK cell receptors, the tumor escape mechanisms that hinder NK cell function, and the evolving field of NK cell-based cancer immunotherapy, highlighting ongoing efforts to develop more effective and targeted cancer treatment strategies.

论文信息

作者
Greppi M、De Franco F、Obino V、Rebaudi F、Goda R、Frumento D、Vita G、Baronti C
第一作者单位
Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.Italy
通讯作者单位
Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address: emanuela.marcenaro@unige.it.Italy
文献类型
综述 · 非美国政府资助研究
期刊
Immunology letters2024 Dec
原文标识
PubMed 39303993 · DOI 10.1016/j.imlet.2024.106932