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

Science immunology

Authors: 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

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.

PMID: 39058763

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