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巨噬细胞作为实体癌潜在免疫治疗靶点

英文原题:Macrophages as a Potential Immunotherapeutic Target in Solid Cancers.

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Macrophages as a Potential Immunotherapeutic Target in Solid Cancers.

PubMed 2022/12/26(内容时间) Vaccines (Basel) Q2 · IF 3.5(JCR 2025)

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中文摘要

过去几十年来癌症免疫治疗的革命已经导致癌症临床治疗的范式转变。迄今为止批准的大多数癌症免疫治疗方案都依赖于调节适应性免疫系统。近年来,靶向固有免疫系统组分的策略和方法因其在靶向实体癌方面的疗效而被广泛认可。巨噬细胞是固有免疫系统的效应细胞,通过其吞噬癌细胞并将肿瘤抗原呈递给适应性免疫细胞的能力,在抗肿瘤免疫的产生中发挥关键作用。

然而,被募集到肿瘤微环境中的巨噬细胞主要发挥促肿瘤作用。几种靶向促肿瘤功能并利用巨噬细胞抗肿瘤特性的策略已在临床前研究中显示出有前景的结果,其中一些也已推进至临床试验。在这篇综述中,我们全面概述了 TAM 的病理生物学及其在实体恶性肿瘤进展中的作用。

我们讨论了 TAM 促进肿瘤进展的各种机制,如炎症、基因组不稳定性、肿瘤生长、癌症干细胞形成、血管生成、EMT 和转移、组织重塑以及免疫抑制等。

此外,我们还讨论了靶向 TAM 的潜在治疗策略,并探讨了如何将巨噬细胞用作下一代免疫治疗工具来治疗实体恶性肿瘤。

展开英文摘要原文

The revolution in cancer immunotherapy over the last few decades has resulted in a paradigm shift in the clinical care of cancer. Most of the cancer immunotherapeutic regimens approved so far have relied on modulating the adaptive immune system.

In recent years, strategies and approaches targeting the components of innate immunity have become widely recognized for their efficacy in targeting solid cancers. Macrophages are effector cells of the innate immune system, which can play a crucial role in the generation of anti-tumor immunity through their ability to phagocytose cancer cells and present tumor antigens to the cells of adaptive immunity.

However, the macrophages that are recruited to the tumor microenvironment predominantly play pro-tumorigenic roles. Several strategies targeting pro-tumorigenic functions and harnessing the anti-tumorigenic properties of macrophages have shown promising results in preclinical studies, and a few of them have also advanced to clinical trials. In this review, we present a comprehensive overview of the pathobiology of TAMs and their role in the progression of solid malignancies.

We discuss various mechanisms through which TAMs promote tumor progression, such as inflammation, genomic instability, tumor growth, cancer stem cell formation, angiogenesis, EMT and metastasis, tissue remodeling, and immunosuppression, etc.

In addition, we also discuss potential therapeutic strategies for targeting TAMs and explore how macrophages can be used as a tool for next-generation immunotherapy for the treatment of solid malignancies.

论文信息

作者
Mishra AK、Banday S、Bharadwaj R、Ali A、Rashid R、Kulshreshtha A、Malonia SK
单位
Department of Molecular, Cell and Cancer Biology, UMass Chan Medical School, Worcester, MA 01605, USA.United States
文献类型
综述
期刊
Vaccines2022 Dec 26
原文标识
PubMed 36679900 · DOI 10.3390/vaccines11010055