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LYVE-1 + macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.
- Source :
-
Developmental cell [Dev Cell] 2023 Sep 11; Vol. 58 (17), pp. 1548-1561.e10. Date of Electronic Publication: 2023 Jul 12. - Publication Year :
- 2023
-
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 <superscript>+</superscript> 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 <superscript>+</superscript> TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8 <superscript>+</superscript> 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Mice
Animals
Macrophages metabolism
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 58
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 37442140
- Full Text :
- https://doi.org/10.1016/j.devcel.2023.06.006