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

Autor:	Anstee JE; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Feehan KT; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Opzoomer JW; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Dean I; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK., Muller HP; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Bahri M; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Cheung TS; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Liakath-Ali K; Centre for Stem Cells and Regenerative Medicine, King's College London, London SE1 9RT, UK., Liu Z; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Choy D; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Caron J; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Sosnowska D; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Beatson R; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Muliaditan T; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., An Z; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Gillett CE; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Lan G; Cancer Research UK Cambridge Research Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK., Zou X; Cancer Research UK Cambridge Research Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK., Watt FM; Centre for Stem Cells and Regenerative Medicine, King's College London, London SE1 9RT, UK., Ng T; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK; UCL Cancer Institute, University College London, London WC1E 6DD, UK., Burchell JM; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK., Kordasti S; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK; Haematology Department, Guy's Hospital, London SE1 9RT, UK., Withers DR; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK., Lawrence T; Centre for Inflammation Biology and Cancer Immunology, School of Immunology & Microbial Sciences, King's College London, London SE1 1UL, UK; Aix Marseille University, CNRS, INSERM, CIML, Marseille, France; Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China., Arnold JN; School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK. Electronic address: james.arnold@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2023 Sep 11; Vol. 58 (17), pp. 1548-1561.e10. Date of Electronic Publication: 2023 Jul 12.
DOI:	10.1016/j.devcel.2023.06.006
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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