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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)1548-1561.e10
JournalDevelopmental Cell
Volume58
Issue number17
Early online date11 Sept 2023
DOIs
Publication statusPublished - 11 Sept 2023

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