巨噬细胞和成纤维细胞是胰腺癌免疫反应的调节器

IF 27.7 1区 医学 Q1 IMMUNOLOGY
Mojdeh Shakiba, David A. Tuveson
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引用次数: 0

摘要

胰腺导管腺癌(PDAC)是为数不多的尚未从免疫疗法中获益的癌症之一。这主要是由于其特有的“冷”肿瘤微环境由癌症相关成纤维细胞(CAFs)、细胞外基质的密集网络和几种免疫细胞类型组成,其中最丰富的是肿瘤相关巨噬细胞(tam)。单细胞和空间技术的进步已经阐明了CAFs和tam的巨大功能异质性,以及它们在肿瘤微环境中的共生关系和合作作用。在这篇综述中,我们概述了CAFs和tam的异质性,它们如何建立免疫抑制微环境以及它们在细胞外基质重塑中的协同作用。最后,我们研究了为什么免疫治疗对PDAC的影响有限,以及对CAFs和tam联合作用的详细分子和空间理解如何对有效治疗的设计至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer

Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers that has yet to benefit from immunotherapies. This is primarily a result of its characteristic ‘cold’ tumor microenvironment composed of cancer-associated fibroblasts (CAFs), a dense network of extracellular matrix and several immune cell types, the most abundant of which are the tumor-associated macrophages (TAMs). Advances in single-cell and spatial technologies have elucidated the vast functional heterogeneity of CAFs and TAMs, their symbiotic relationship and their cooperative role in the tumor microenvironment. In this Review, we provide an overview of the heterogeneity of CAFs and TAMs, how they establish an immunosuppressive microenvironment and their collaboration in the remodeling of the extracellular matrix. Finally, we examine why the impact of immunotherapy in PDAC has been limited and how a detailed molecular and spatial understanding of the combined role of CAFs and TAMs is paramount to the design of effective therapies.

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来源期刊
Nature Immunology
Nature Immunology 医学-免疫学
CiteScore
40.00
自引率
2.30%
发文量
248
审稿时长
4-8 weeks
期刊介绍: Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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