生物物理生态位对肝癌中肿瘤相关巨噬细胞的影响

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-10-30 eCollection Date: 2024-11-01 DOI:10.1097/HC9.0000000000000569
Ying Zhang, Ying Rao, Jiahuan Lu, Jiyu Wang, Dai Fei Elmer Ker, Jingying Zhou, Dan Michelle Wang
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引用次数: 0

摘要

肝癌是最常见的原发性肝癌,也是全球癌症相关死亡的主要原因。尽管以程序性细胞死亡 1 或程序性细胞死亡 1 配体 1 为靶点的免疫检查点抑制剂(ICIs)所带来的免疫疗法的进步彻底改变了对 HCC 的治疗,但大多数疗法仍无益于 HCC 的治疗。越来越多的证据表明,HCC 中具有强大免疫抑制作用的肿瘤微环境对 ICI 的疗效构成了巨大挑战。作为肿瘤微环境的关键组成部分,肿瘤相关巨噬细胞(TAMs)在 HCC 的发生、发展和 ICI 低反应性中发挥着至关重要的作用。从机理上讲,TAM 可以促进癌症的侵袭和转移、血管生成、上皮-间质转化、干性维持,最重要的是,还能促进免疫抑制。因此,靶向 TAM 是提高 ICI 对 HCC 患者疗效的一个机会。以往的研究主要关注影响巨噬细胞的生化线索,而新出现的证据则强调了生物物理信号的关键作用,如基底硬度、地形和外力。在这篇综述中,我们总结了肿瘤微环境中的生物物理特征对 HCC 发病和进展过程中 TAMs 表型和功能的调节作用。我们还探讨了可能的机制,并讨论了操纵生物物理线索调节 TAM 治疗 HCC 的潜力。通过深入了解巨噬细胞如何感知机械力并对其做出反应,我们有可能开辟出一条治疗癌症的联合免疫疗法之路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The influence of biophysical niche on tumor-associated macrophages in liver cancer.

HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.

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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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