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M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment

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M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment. / Van Overmeire, Eva; Stijlemans, Benoît; Heymann, Felix; Keirsse, Jiri; Morias, Yannick; Elkrim, Yvon; Brys, Lea; Abels, Chloé; Lahmar, Qods; Ergen, Can; Vereecke, Lars; Tacke, Frank; De Baetselier, Patrick; Van Ginderachter, Jo A; Laoui, Damya.

In: CANCER RES, Vol. 76, No. 1, 01.01.2016, p. 35-42.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Van Overmeire, E, Stijlemans, B, Heymann, F, Keirsse, J, Morias, Y, Elkrim, Y, Brys, L, Abels, C, Lahmar, Q, Ergen, C, Vereecke, L, Tacke, F, De Baetselier, P, Van Ginderachter, JA & Laoui, D 2016, 'M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment', CANCER RES, vol. 76, no. 1, pp. 35-42. https://doi.org/10.1158/0008-5472.CAN-15-0869

APA

Van Overmeire, E., Stijlemans, B., Heymann, F., Keirsse, J., Morias, Y., Elkrim, Y., Brys, L., Abels, C., Lahmar, Q., Ergen, C., Vereecke, L., Tacke, F., De Baetselier, P., Van Ginderachter, J. A., & Laoui, D. (2016). M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment. CANCER RES, 76(1), 35-42. https://doi.org/10.1158/0008-5472.CAN-15-0869

Vancouver

Van Overmeire E, Stijlemans B, Heymann F, Keirsse J, Morias Y, Elkrim Y et al. M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment. CANCER RES. 2016 Jan 1;76(1):35-42. https://doi.org/10.1158/0008-5472.CAN-15-0869

Bibtex

@article{f0214fbb39454ef7a7eb83eae8060dbc,
title = "M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment",
abstract = "Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.",
keywords = "Animals, Antibodies, Monoclonal, Carcinoma, Lewis Lung, Cell Differentiation, Cell Polarity, Female, Macrophage Colony-Stimulating Factor, Macrophages, Mammary Neoplasms, Experimental, Mice, Mice, Inbred C57BL, Monocytes, Receptors, Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Signal Transduction, Tumor Microenvironment, Journal Article, Research Support, Non-U.S. Gov't",
author = "{Van Overmeire}, Eva and Beno{\^i}t Stijlemans and Felix Heymann and Jiri Keirsse and Yannick Morias and Yvon Elkrim and Lea Brys and Chlo{\'e} Abels and Qods Lahmar and Can Ergen and Lars Vereecke and Frank Tacke and {De Baetselier}, Patrick and {Van Ginderachter}, {Jo A} and Damya Laoui",
note = "{\textcopyright}2015 American Association for Cancer Research.",
year = "2016",
month = jan,
day = "1",
doi = "10.1158/0008-5472.CAN-15-0869",
language = "English",
volume = "76",
pages = "35--42",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment

AU - Van Overmeire, Eva

AU - Stijlemans, Benoît

AU - Heymann, Felix

AU - Keirsse, Jiri

AU - Morias, Yannick

AU - Elkrim, Yvon

AU - Brys, Lea

AU - Abels, Chloé

AU - Lahmar, Qods

AU - Ergen, Can

AU - Vereecke, Lars

AU - Tacke, Frank

AU - De Baetselier, Patrick

AU - Van Ginderachter, Jo A

AU - Laoui, Damya

N1 - ©2015 American Association for Cancer Research.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.

AB - Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.

KW - Animals

KW - Antibodies, Monoclonal

KW - Carcinoma, Lewis Lung

KW - Cell Differentiation

KW - Cell Polarity

KW - Female

KW - Macrophage Colony-Stimulating Factor

KW - Macrophages

KW - Mammary Neoplasms, Experimental

KW - Mice

KW - Mice, Inbred C57BL

KW - Monocytes

KW - Receptors, Colony-Stimulating Factor

KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

KW - Signal Transduction

KW - Tumor Microenvironment

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1158/0008-5472.CAN-15-0869

DO - 10.1158/0008-5472.CAN-15-0869

M3 - SCORING: Journal article

C2 - 26573801

VL - 76

SP - 35

EP - 42

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 1

ER -