Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis.

Autor:	Dalla E; Division of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Papanicolaou M; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Park MD; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Barth N; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Research UK Edinburgh Centre, University of Edinburgh, Edinburgh, UK., Hou R; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia., Segura-Villalobos D; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Valencia Salazar L; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Sun D; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Forrest ARR; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia., Casanova-Acebes M; Cancer Immunity Laboratory, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain., Entenberg D; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Merad M; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Aguirre-Ghiso JA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA. Electronic address: julio.aguirre-ghiso@einsteinmed.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Nov 14; Vol. 187 (23), pp. 6631-6648.e20. Date of Electronic Publication: 2024 Oct 07.
DOI:	10.1016/j.cell.2024.09.016
Abstrakt:	Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-β2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-βRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-β2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-β2 receptor. Restoring TGF-βRIII in aggressive cells reinstates TGF-β2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-β2 signaling allows cancer cells to overcome macrophage-mediated growth suppression. Competing Interests: Declaration of interests J.A.A.-G. is a scientific co-founder and scientific advisory board member of and an equity owner in HiberCell and receives financial compensation as a consultant for HiberCell, a Mount Sinai spin-off company focused on the research and development of therapeutics that prevent or delay the recurrence of cancer. J.A.A.-G. is also a consultant for Astrin Biosciences and Chief Mission Advisor for the Samuel Waxman Cancer Research Foundation. M.M. serves on the scientific advisory board of and holds stock from Compugen Inc., Myeloid Therapeutics Inc., Morphic Therapeutic Inc., Asher Bio Inc., Dren Bio Inc., Nirogy Inc., Oncoresponse Inc., Owkin Inc., Pionyr Inc., OSE Inc., and Larkspur Inc. M.M. serves on the scientific advisory board of Innate Pharma Inc., DBV Inc., and Genenta Inc. M.M. receives funding for contracted research from Regeneron Inc. and Boerhinger Ingelheim Inc. M.M. is a named co-inventor on an issued patent for multiplex immunohistochemistry to characterize tumors and treatment responses. The technology is filed through Icahn School of Medicine at Mount Sinai (ISMMS) and is currently unlicensed. This technology was used to evaluate tissue in this study, and the results could impact the value of this technology. M.M. has ownership interest (<5%) in Compugen Inc., Morphic Therapeutic Inc., Myeloid Therapeutics Inc., Asher Bio Inc., Dren Bio Inc., Nirogy Inc., Owkin Inc., Pionyr Inc., and Larkspur Inc. M.M. and J.A.A.-G. declare no ownership interest greater than or equal to 5%. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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