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

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

doi:10.1126/sciimmunol.adk3981

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

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 ChakarovZhaoyuan 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	eadk3981
Journal	Science Immunology
Volume	9
Issue number	97
DOIs	https://doi.org/10.1126/sciimmunol.adk3981
Publication status	Published - 1 Jul 2024

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Dunsmore, G., Guo, W., Li, Z., Bejarano, D. A., Pai, R., Yang, K., Kwok, I., Tan, L., Ng, M., De La Calle Fabregat, C., Yatim, A., Bougouin, A., Mulder, K., Thomas, J., Villar, J., Bied, M., Kloeckner, B., Dutertre, C. A., Gessain, G., ... Ginhoux, F. (2024). Timing and location dictate monocyte fate and their transition to tumor-associated macrophages. Science Immunology, 9(97), Article eadk3981. https://doi.org/10.1126/sciimmunol.adk3981

@article{705d89a3d02b4c4db2b541665b2aca5a,

title = "Timing and location dictate monocyte fate and their transition to tumor-associated macrophages",

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.",

author = "Garett Dunsmore and Wei Guo and Ziyi Li and Bejarano, {David Alejandro} and Rhea Pai and Katharine Yang and Immanuel Kwok and Leonard Tan and Melissa Ng and {De La Calle Fabregat}, Carlos and Aline Yatim and Antoine Bougouin and Kevin Mulder and Jake Thomas and Javiera Villar and Mathilde Bied and Benoit Kloeckner and Dutertre, {Charles Antoine} and Gr{\'e}goire Gessain and Svetoslav Chakarov and Zhaoyuan Liu and Scoazec, {Jean Yves} and Lennon-Dumenil, {Ana Maria} and Thomas Marichal and Catherine Saut{\`e}s-Fridman and Fridman, {Wolf Herman} and Ankur Sharma and Bing Su and Andreas Schlitzer and Ng, {Lai Guan} and Camille Bl{\'e}riot and Florent Ginhoux",

note = "Publisher Copyright: copyright {\textcopyright} 2024 the authors, some rights reserved",

year = "2024",

month = jul,

day = "1",

doi = "10.1126/sciimmunol.adk3981",

language = "English",

volume = "9",

journal = "Science Immunology",

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Dunsmore, G, Guo, W, Li, Z, Bejarano, DA, Pai, R, Yang, K, Kwok, I, Tan, L, Ng, M, De La Calle Fabregat, C, Yatim, A, Bougouin, A, Mulder, K, Thomas, J, Villar, J, Bied, M, Kloeckner, B, Dutertre, CA, Gessain, G, Chakarov, S, Liu, Z, Scoazec, JY, Lennon-Dumenil, AM, Marichal, T, Sautès-Fridman, C, Fridman, WH, Sharma, A, Su, B, Schlitzer, A, Ng, LG, Blériot, C & Ginhoux, F 2024, 'Timing and location dictate monocyte fate and their transition to tumor-associated macrophages', Science Immunology, vol. 9, no. 97, eadk3981. https://doi.org/10.1126/sciimmunol.adk3981

TY - JOUR

T1 - Timing and location dictate monocyte fate and their transition to tumor-associated macrophages

AU - Dunsmore, Garett

AU - Guo, Wei

AU - Li, Ziyi

AU - Bejarano, David Alejandro

AU - Pai, Rhea

AU - Yang, Katharine

AU - Kwok, Immanuel

AU - Tan, Leonard

AU - Ng, Melissa

AU - De La Calle Fabregat, Carlos

AU - Yatim, Aline

AU - Bougouin, Antoine

AU - Mulder, Kevin

AU - Thomas, Jake

AU - Villar, Javiera

AU - Bied, Mathilde

AU - Kloeckner, Benoit

AU - Dutertre, Charles Antoine

AU - Gessain, Grégoire

AU - Chakarov, Svetoslav

AU - Liu, Zhaoyuan

AU - Scoazec, Jean Yves

AU - Lennon-Dumenil, Ana Maria

AU - Marichal, Thomas

AU - Sautès-Fridman, Catherine

AU - Fridman, Wolf Herman

AU - Sharma, Ankur

AU - Su, Bing

AU - Schlitzer, Andreas

AU - Ng, Lai Guan

AU - Blériot, Camille

AU - Ginhoux, Florent

PY - 2024/7/1

Y1 - 2024/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85199935936&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.adk3981

DO - 10.1126/sciimmunol.adk3981

M3 - Article

C2 - 39058763

AN - SCOPUS:85199935936

SN - 2470-9468

VL - 9

JO - Science Immunology

JF - Science Immunology

IS - 97

M1 - eadk3981

ER -

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

Abstract

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