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恶性肿瘤微环境中单克隆抗体对 NK 细胞的再激活

英文原题:Reactivation of natural killer cells with monoclonal antibodies in the microenvironment of malignant neoplasms.

查看英文原题

Reactivation of natural killer cells with monoclonal antibodies in the microenvironment of malignant neoplasms.

PubMed 2023/01/12(内容时间) J Cancer Res Clin Oncol Q2 · IF 3.3(JCR 2025)

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中文摘要

NK 细胞在抗肿瘤免疫反应中起着关键作用,因为它们能够通过细胞毒活性及其他方式摧毁靶细胞。然而,在肿瘤微环境中,这种反应受到抑制,其中严重缺氧的环境和多种抑制性分子与NK细胞结合,触发无反应状态。抑制性受体如PD-1、NK2GA、KIR、TIGIT和LAG-3已被发现与多种癌症类型中NK细胞的抑制相关。与这些受体结合会导致细胞毒性丧失、增殖和代谢率降低,甚至凋亡。虽然这些受体对于避免自身免疫很重要,但在恶性肿瘤等病理环境中,它们不利于个体免疫系统对抗癌细胞。使用单克隆抗体阻断这些受体通过防止NK细胞被抑制,有助于癌症治疗。在这篇综述中,总结了NK细胞抑制和激活对癌症治疗的影响,并概述了通过单克隆抗体阻断抑制性通路的情况。

展开英文摘要原文

Natural killer cells are critical players in the antitumor immune response due to their ability to destroy target cells through cytotoxic activity and other means.

However, this response is inhibited in the tumor microenvironment, where a crippling hypoxic environment and several inhibitory molecules bind to NK cells to trigger an anergic state. Inhibitory receptors such as PD-1, NK2GA, KIR, TIGIT, and LAG-3 have been associated with inhibition of NK cells in multiple cancer types. Binding to these receptors leads to loss of cytotoxicity, lower proliferation and metabolic rates, and even apoptosis.

While these receptors are important for avoiding auto-immunity, in a pathological setting like malignant neoplasms they are disadvantageous for the individual's immune system to combat cancer cells. The use of monoclonal antibodies to block these receptors contributes to cancer therapy by preventing the inhibition of NK cells. In this review, the impact of NK cell inhibition and activation on cancer therapy was summarized and an overview of the blockade of inhibitory pathways by monoclonal antibodies was provided.

论文信息

作者
Soldi LR、Silva VLC、Rabelo DH、Uehara IA、Silva MJB
第一作者单位
Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil.Brazil
通讯作者单位
Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil. majbsilva@gmail.com.Brazil
文献类型
综述
期刊
Journal of cancer research and clinical oncology2023 Aug
原文标识
PubMed 36633682 · DOI 10.1007/s00432-023-04575-8