Immune cells in cancer
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It is 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.
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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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@article{Dunsmore2024Timing,
title = {Timing and location dictate monocyte fate and their transition to tumor-associated macrophages},
author = {Garett Dunsmore and Wei Guo and Ziyi Li and David Alejandro Bejarano and Rhea Pai and Katharine Yang and Immanuel Kwok and Leonard Tan and Melissa Ng and Carlos de la Calle‐Fabregat and Aline Yatim and Antoine Bougoüin and Kevin Mulder and Jake Thomas and Javiera Villar and Mathilde Bied and Benoit Kloeckner and Charles‐Antoine Dutertre and Grégoire Gessain and Svetoslav Chakarov and Zhaoyuan Liu and Jean‐Yves Scoazec and Ana‐Maria Lennon‐Duménil and Thomas Marichal and Catherine Sautès‐Fridman and Wolf H. Fridman and Ankur Sharma and Bing Su and Andreas Schlitzer and Lai Guan Ng and Camille Blériot and Florent Ginhoux},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adk3981},
url = {https://doi.org/10.1126/sciimmunol.adk3981}
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