Timing and location dictate monocyte fate and their transition to tumor-associated macrophages

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-07-26 DOI:10.1126/sciimmunol.adk3981

Garett Dunsmore, Wei Guo, Ziyi Li, David Alejandro Bejarano, Rhea Pai, Katharine Yang, Immanuel Kwok, Leonard Tan, Melissa Ng, Carlos De La Calle Fabregat, Aline Yatim, Antoine Bougouin, Kevin Mulder, Jake Thomas, Javiera Villar, Mathilde Bied, Benoit Kloeckner, Charles-Antoine Dutertre, Grégoire Gessain, Svetoslav Chakarov, Zhaoyuan Liu, Jean-Yves Scoazec, Ana-Maria Lennon-Dumenil, Thomas Marichal, Catherine Sautès-Fridman, Wolf Herman Fridman, Ankur Sharma, Bing Su, Andreas Schlitzer, Lai Guan Ng, Camille Blériot, Florent Ginhoux

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引用次数: 0

Abstract

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition. We revealed that monocytes differentiate first into a transient intermediate population of TAMs that generates two longer-lived lineages of terminally differentiated TAMs with distinct gene expression profiles, phenotypes, and intratumoral localization. Transcriptome datasets and tumor samples from patients with PDAC evidenced parallel TAM populations in humans and their prognostic associations. These insights will support the design of new therapeutic strategies targeting TAMs in PDAC.

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时间和地点决定了单核细胞的命运及其向肿瘤相关巨噬细胞的转变。

肿瘤相关巨噬细胞（TAMs）是一种异质性细胞群，其表型和功能是由尚未完全清楚的因素形成的。在这里，我们想知道 TAMs 是何时何地从血液单核细胞中产生的，以及它们在肿瘤发生过程中是如何演变的。我们在诱导性单核细胞命运图谱小鼠中诱发了胰腺导管腺癌（PDAC），并结合单细胞转录组学和高维流式细胞术分析了单核细胞向TAM的转变。我们发现，单核细胞首先分化成一过性的中间TAMs群体，然后产生两个寿命较长的终末分化TAMs品系，它们具有不同的基因表达谱、表型和瘤内定位。转录组数据集和 PDAC 患者的肿瘤样本证明了人类中平行的 TAM 群体及其与预后的关联。这些见解将有助于设计针对 PDAC 中 TAMs 的新治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.