文章：

肿瘤微环境中DNAM-1介导的NK细胞抗癌应答失调机制研究

Dysregulation of DNAM-1-Mediated NK Cell Anti-Cancer Responses in the Tumor Microenvironment

原文发布日期：18 September 2023

DOI: 10.3390/cancers15184616

类型: Article

开放获取: 是

英文摘要：

NK cells play a pivotal role in anti-cancer immune responses, thanks to the expression of a wide array of inhibitory and activating receptors that regulate their cytotoxicity against transformed cells while preserving healthy cells from lysis. However, NK cells exhibit severe dysfunction in the tumor microenvironment, mainly due to the reduction of activating receptors and the induction or increased expression of inhibitory checkpoint receptors. An activating receptor that plays a central role in tumor recognition is the DNAM-1 receptor. It recognizes PVR and Nectin2 adhesion molecules, which are frequently overexpressed on the surface of cancerous cells. These ligands are also able to trigger inhibitory signals via immune checkpoint receptors that are upregulated in the tumor microenvironment and can counteract DNAM-1 activation. Among them, TIGIT has recently gained significant attention, since its targeting results in improved anti-tumor immune responses. This review aims to summarize how the recognition of PVR and Nectin2 by paired co-stimulatory/inhibitory receptors regulates NK cell-mediated clearance of transformed cells. Therapeutic approaches with the potential to reverse DNAM-1 dysfunction in the tumor microenvironment will be also discussed.

摘要翻译： 

自然杀伤细胞在抗癌免疫应答中扮演着关键角色，这得益于其表达的一系列抑制性与活化性受体，这些受体既能调控其对转化细胞的杀伤作用，又能保护健康细胞免受裂解。然而，在肿瘤微环境中，自然杀伤细胞表现出严重功能障碍，主要源于活化性受体的减少以及抑制性检查点受体的诱导或表达增加。DNAM-1受体作为在肿瘤识别中起核心作用的活化性受体，能够识别癌细胞表面常过度表达的PVR和Nectin2黏附分子。这些配体同时也能通过肿瘤微环境中上调的免疫检查点受体触发抑制信号，从而抵消DNAM-1的活化作用。其中，TIGIT受体因靶向治疗可增强抗肿瘤免疫应答而备受关注。本文旨在总结配对的共刺激/抑制受体对PVR和Nectin2的识别如何调控自然杀伤细胞介导的转化细胞清除，并将探讨可能逆转肿瘤微环境中DNAM-1功能障碍的治疗策略。

原文链接：

Dysregulation of DNAM-1-Mediated NK Cell Anti-Cancer Responses in the Tumor Microenvironment