LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

Joanne E. Anstee; Karen T. Feehan; James W. Opzoomer; Isaac Dean; Henrike P. Muller; Meriem Bahri; Tik Shing Cheung; Kifayathullah Liakath-Ali; Ziyan Liu; Desmond Choy; Jonathan Caron; Dominika Sosnowska; Richard Beatson; Tamara Muliaditan; Zhengwen An; Cheryl E. Gillett; Guocheng Lan; Xiangang Zou; Fiona M. Watt; Tony Ng; Joy M. Burchell; Shahram Kordasti; David R. Withers; Toby Lawrence; James N. Arnold

doi:10.1016/j.devcel.2023.06.006

LYVE-1⁺ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

Joanne E. Anstee, Karen T. Feehan, James W. Opzoomer, Isaac Dean, Henrike P. Muller, Meriem Bahri, Tik Shing Cheung, Kifayathullah Liakath-Ali, Ziyan Liu, Desmond Choy, Jonathan Caron, Dominika Sosnowska, Richard Beatson, Tamara Muliaditan, Zhengwen An, Cheryl E. Gillett, Guocheng Lan, Xiangang Zou, Fiona M. Watt, Tony NgJoy M. Burchell, Shahram Kordasti, David R. Withers, Toby Lawrence, James N. Arnold

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Abstract

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1⁺ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1⁺ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8⁺ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.

Original language	English
Pages (from-to)	1548-1561.e10
Number of pages	24
Journal	Developmental Cell
Volume	58
Issue number	17
Early online date	12 Jul 2023
DOIs	https://doi.org/10.1016/j.devcel.2023.06.006
Publication status	Published - 11 Sept 2023

Bibliographical note

Acknowledgments:
The authors thank Dr. Yasmin Haque (KCL) and the NIHR BRC flow cytometry platform at Guy’s and St Thomas’ Biomedical Research Centre for cell sorting and flow cytometry assistance and Dr. James Levitt and the Nikon Imaging Centre (KCL) for the use of their facilities and assistance with confocal microscopy analyses. The authors would like to thank Drs. Paul Lavender, Tracey Mitchell, Gilbert Fruhwirth (KCL), and Professor Awen Gallimore (University of Cardiff) for useful discussion/advice/support; Miss Rosamond Nuamah (KCL) for running the microarray; and Mr. Stuart Newman (KCL) for help with the rederivation of the HO-1Luc/EGFP reporter mouse. The authors thank Professor George Kollias (University of Athens) for the use of the Hmox1fl/fl allele mice. The authors would like to thank Miss Jiaying Yao for the initial optimization of the focal-point macrophage migration assay. This work was funded by the following grants: Cancer Research UK grant DCRPGF\100009 (J.N.A.), European Research Council grant 335326 (J.N.A.), Cancer Research Institute/Wade F.B. Thompson CLIP grant (CRI3645) (J.N.A.), Medical Research Council grant MR/N013700/1 (J.E.A.), Medical Research Council grant MR/PO18823/1 (F.M.W.), Wellcome Trust grant 206439/Z/17/Z (F.M.W.), and Cancer Research UK grant C54019/A27535 (D.R.W.). The research was supported by the Cancer Research UK King’s Health Partners Centre and Experimental Cancer Medicine Centre at King’s College London and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Copyright:
© 2023 The Author(s). Published by Elsevier Inc.

Keywords

Mice
Animals
Neoplasms/pathology
Macrophages/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.devcel.2023.06.006Licence: Creative Commons: Attribution (CC BY)

AnsteeJ2023LYVEFinal published version, 6.49 MBLicence: Creative Commons: Attribution (CC BY)

Revealing anti-tumour T cell recruitment and recirculation in vivo to optimise therapeutic intervention.
Withers, D.
Cancer Research Uk
1/02/19 → 31/01/22
Project: Research

Cite this

Anstee, J. E., Feehan, K. T., Opzoomer, J. W., Dean, I., Muller, H. P., Bahri, M., Cheung, T. S., Liakath-Ali, K., Liu, Z., Choy, D., Caron, J., Sosnowska, D., Beatson, R., Muliaditan, T., An, Z., Gillett, C. E., Lan, G., Zou, X., Watt, F. M., ... Arnold, J. N. (2023). LYVE-1⁺ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer. Developmental Cell, 58(17), 1548-1561.e10. https://doi.org/10.1016/j.devcel.2023.06.006

@article{aeb9589ac09d445f97ea0fe0b6165c21,

title = "LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer",

abstract = "Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular {"}nest{"} structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1+ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1+ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8+ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.",

keywords = "Mice, Animals, Neoplasms/pathology, Macrophages/metabolism",

author = "Anstee, {Joanne E.} and Feehan, {Karen T.} and Opzoomer, {James W.} and Isaac Dean and Muller, {Henrike P.} and Meriem Bahri and Cheung, {Tik Shing} and Kifayathullah Liakath-Ali and Ziyan Liu and Desmond Choy and Jonathan Caron and Dominika Sosnowska and Richard Beatson and Tamara Muliaditan and Zhengwen An and Gillett, {Cheryl E.} and Guocheng Lan and Xiangang Zou and Watt, {Fiona M.} and Tony Ng and Burchell, {Joy M.} and Shahram Kordasti and Withers, {David R.} and Toby Lawrence and Arnold, {James N.}",

note = "Acknowledgments: The authors thank Dr. Yasmin Haque (KCL) and the NIHR BRC flow cytometry platform at Guy{\textquoteright}s and St Thomas{\textquoteright} Biomedical Research Centre for cell sorting and flow cytometry assistance and Dr. James Levitt and the Nikon Imaging Centre (KCL) for the use of their facilities and assistance with confocal microscopy analyses. The authors would like to thank Drs. Paul Lavender, Tracey Mitchell, Gilbert Fruhwirth (KCL), and Professor Awen Gallimore (University of Cardiff) for useful discussion/advice/support; Miss Rosamond Nuamah (KCL) for running the microarray; and Mr. Stuart Newman (KCL) for help with the rederivation of the HO-1Luc/EGFP reporter mouse. The authors thank Professor George Kollias (University of Athens) for the use of the Hmox1fl/fl allele mice. The authors would like to thank Miss Jiaying Yao for the initial optimization of the focal-point macrophage migration assay. This work was funded by the following grants: Cancer Research UK grant DCRPGF\100009 (J.N.A.), European Research Council grant 335326 (J.N.A.), Cancer Research Institute/Wade F.B. Thompson CLIP grant (CRI3645) (J.N.A.), Medical Research Council grant MR/N013700/1 (J.E.A.), Medical Research Council grant MR/PO18823/1 (F.M.W.), Wellcome Trust grant 206439/Z/17/Z (F.M.W.), and Cancer Research UK grant C54019/A27535 (D.R.W.). The research was supported by the Cancer Research UK King{\textquoteright}s Health Partners Centre and Experimental Cancer Medicine Centre at King{\textquoteright}s College London and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Copyright: {\textcopyright} 2023 The Author(s). Published by Elsevier Inc.",

year = "2023",

month = sep,

day = "11",

doi = "10.1016/j.devcel.2023.06.006",

language = "English",

volume = "58",

pages = "1548--1561.e10",

journal = "Developmental Cell",

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Anstee, JE, Feehan, KT, Opzoomer, JW, Dean, I, Muller, HP, Bahri, M, Cheung, TS, Liakath-Ali, K, Liu, Z, Choy, D, Caron, J, Sosnowska, D, Beatson, R, Muliaditan, T, An, Z, Gillett, CE, Lan, G, Zou, X, Watt, FM, Ng, T, Burchell, JM, Kordasti, S, Withers, DR, Lawrence, T & Arnold, JN 2023, 'LYVE-1⁺ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer', Developmental Cell, vol. 58, no. 17, pp. 1548-1561.e10. https://doi.org/10.1016/j.devcel.2023.06.006

TY - JOUR

T1 - LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

AU - Anstee, Joanne E.

AU - Feehan, Karen T.

AU - Opzoomer, James W.

AU - Dean, Isaac

AU - Muller, Henrike P.

AU - Bahri, Meriem

AU - Cheung, Tik Shing

AU - Liakath-Ali, Kifayathullah

AU - Liu, Ziyan

AU - Choy, Desmond

AU - Caron, Jonathan

AU - Sosnowska, Dominika

AU - Beatson, Richard

AU - Muliaditan, Tamara

AU - An, Zhengwen

AU - Gillett, Cheryl E.

AU - Lan, Guocheng

AU - Zou, Xiangang

AU - Watt, Fiona M.

AU - Ng, Tony

AU - Burchell, Joy M.

AU - Kordasti, Shahram

AU - Withers, David R.

AU - Lawrence, Toby

AU - Arnold, James N.

N1 - Acknowledgments: The authors thank Dr. Yasmin Haque (KCL) and the NIHR BRC flow cytometry platform at Guy’s and St Thomas’ Biomedical Research Centre for cell sorting and flow cytometry assistance and Dr. James Levitt and the Nikon Imaging Centre (KCL) for the use of their facilities and assistance with confocal microscopy analyses. The authors would like to thank Drs. Paul Lavender, Tracey Mitchell, Gilbert Fruhwirth (KCL), and Professor Awen Gallimore (University of Cardiff) for useful discussion/advice/support; Miss Rosamond Nuamah (KCL) for running the microarray; and Mr. Stuart Newman (KCL) for help with the rederivation of the HO-1Luc/EGFP reporter mouse. The authors thank Professor George Kollias (University of Athens) for the use of the Hmox1fl/fl allele mice. The authors would like to thank Miss Jiaying Yao for the initial optimization of the focal-point macrophage migration assay. This work was funded by the following grants: Cancer Research UK grant DCRPGF\100009 (J.N.A.), European Research Council grant 335326 (J.N.A.), Cancer Research Institute/Wade F.B. Thompson CLIP grant (CRI3645) (J.N.A.), Medical Research Council grant MR/N013700/1 (J.E.A.), Medical Research Council grant MR/PO18823/1 (F.M.W.), Wellcome Trust grant 206439/Z/17/Z (F.M.W.), and Cancer Research UK grant C54019/A27535 (D.R.W.). The research was supported by the Cancer Research UK King’s Health Partners Centre and Experimental Cancer Medicine Centre at King’s College London and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Copyright: © 2023 The Author(s). Published by Elsevier Inc.

PY - 2023/9/11

Y1 - 2023/9/11

N2 - Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1+ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1+ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8+ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.

AB - Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1+ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1+ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8+ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.

KW - Mice

KW - Animals

KW - Neoplasms/pathology

KW - Macrophages/metabolism

U2 - 10.1016/j.devcel.2023.06.006

DO - 10.1016/j.devcel.2023.06.006

M3 - Article

C2 - 37442140

SN - 1534-5807

VL - 58

SP - 1548-1561.e10

JO - Developmental Cell

JF - Developmental Cell

IS - 17

ER -