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肿瘤相关成纤维细胞与 NK 细胞和树突状细胞的串扰与通讯:肿瘤免疫治疗的新前沿与未揭示的机遇

英文原题:Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy.

查看英文原题

Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy.

PubMed 2024/10/15(内容时间) Cancer Treat Rev Q1 · IF 10.6(JCR 2025)

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中文摘要

自然杀伤(NK)细胞和树突状细胞(DC)是抗癌免疫应答的关键介质。除各自作用外,NK 细胞与 DC 之间还存在细胞间串扰,这对启动和协调抗癌适应性免疫至关重要。

然而,在肿瘤微环境(TME)中,NK 细胞和 DC 活性常受损。近期,人们高度关注 TME 的主要组成之一癌症相关成纤维细胞(CAF);CAF 不仅促进细胞外基质(ECM)沉积和肿瘤进展,也抑制免疫细胞功能。目前已明确,CAF 可阻止 T 细胞进入肿瘤巢并调节其细胞毒性。相比之下,人们对 CAF 与 NK 细胞和 DC 的相互作用知之甚少。本综述描述 CAF 通过在成人实体瘤 TME 中分泌和表达多种介质而与 NK 细胞及 DC 相互作用的情况,并详细概述靶向基质因子(单独使用或与免疫检查点抑制剂免疫疗法联合使用)的在研临床研究。

最后,讨论目前选择性清除有害 CAF 的策略,以及更好理解 CAF 与 NK 细胞和 DC 相互作用的方法。

展开英文摘要原文

Natural killer (NK) cells and dendritic cells (DCs) are critical mediators of anti-cancer immune responses.

In addition to their individual roles, NK cells and DCs are involved in intercellular crosstalk which is essential for the initiation and coordination of adaptive immunity against cancer.

However, NK cell and DC activity is often compromised in the tumor microenvironment (TME). Recently, much attention has been paid to one of the major components of the TME, the cancer-associated fibroblasts (CAFs), which not only contribute to extracellular matrix (ECM) deposition and tumor progression but also suppress immune cell functions.

It is now well established that CAFs support T cell exclusion from tumor nests and regulate their cytotoxic activity. In contrast, little is currently known about their interaction with NK cells, and DCs. In this review, we describe the interaction of CAFs with NK cells and DCs, by secreting and expressing various mediators in the TME of adult solid tumors.

We also provide a detailed overview of ongoing clinical studies evaluating the targeting of stromal factors alone or in combination with immunotherapy based on immune checkpoint inhibitors.

Finally, we discuss currently available strategies for the selective depletion of detrimental CAFs and for a better understanding of their interaction with NK cells and DCs.

论文信息

作者
Ielpo S、Barberini F、Dabbagh Moghaddam F、Pesce S、Cencioni C、Spallotta F、De Ninno A、Businaro L
第一作者单位
Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.Italy
通讯作者单位
Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address: Ombretta.Melaiu@uniroma2.it.Italy
文献类型
综述
期刊
Cancer treatment reviews2024 Dec
原文标识
PubMed 39442289 · DOI 10.1016/j.ctrv.2024.102843