Article Dans Une Revue Science Immunology Année : 2024

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

Wei Guo
David Alejandro Bejarano
Katharine Yang
Immanuel Kwok
Leonard Tan
Melissa Ng
Aline Yatim
  • Fonction : Auteur
Jake Thomas
Svetoslav Chakarov
Zhaoyuan Liu
Ana-Maria Lennon-Dumenil
Wolf Herman Fridman
Ankur Sharma
Lai Guan Ng

Résumé

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 intra tumoral 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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hal-04728984 , version 1 (05-02-2025)

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Garett Dunsmore, Wei Guo, Ziyi Li, David Alejandro Bejarano, Rhea Pai, et al.. Timing and location dictate monocyte fate and their transition to tumor-associated macrophages. Science Immunology, 2024, 9 (97), ⟨10.1126/sciimmunol.adk3981⟩. ⟨hal-04728984⟩
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