A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features.

Autor:	Klughammer J; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. klughammer@genzentrum.lmu.de.; Gene Center and Department of Biochemistry, Ludwig Maximilians Universität München, Munich, Germany. klughammer@genzentrum.lmu.de., Abravanel DL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. daniel_abravanel@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. daniel_abravanel@dfci.harvard.edu., Segerstolpe Å; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Blosser TR; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA., Goltsev Y; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Cui Y; Department of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA., Goodwin DR; Department of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA., Sinha A; Department of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA., Ashenberg O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Slyper M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Vigneau S; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Jané-Valbuena J; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Alon S; Department of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.; Faculty of Engineering, Gonda Brain Research Center and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel., Caraccio C; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Chen J; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Cohen O; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Guiron University, Beersheba, Israel., Cullen N; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., DelloStritto LK; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Dionne D; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Files J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Frangieh A; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Helvie K; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Hughes ME; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Inga S; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Kanodia A; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Lako A; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., MacKichan C; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Mages S; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Gene Center and Department of Biochemistry, Ludwig Maximilians Universität München, Munich, Germany., Moriel N; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel., Murray E; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Napolitano S; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Nguyen K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Nitzan M; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.; Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem, Israel.; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Ortiz R; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Patel M; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Pfaff KL; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Porter CBM; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Rotem A; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.; AstraZeneca R&D, Boston, MA, USA., Strauss S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Strasser R; Gene Center and Department of Biochemistry, Ludwig Maximilians Universität München, Munich, Germany., Thorner AR; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Turner M; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA., Wakiro I; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Waldman J; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Wu J; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Gómez Tejeda Zañudo J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Zhang D; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Lin NU; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Tolaney SM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Winer EP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Boyden ES; Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.; K. Lisa Yang Center for Bionics, Massachusetts Institute of Technology, Cambridge, MA, USA., Chen F; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Nolan GP; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Rodig SJ; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA., Zhuang X; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA.; Department of Physics, Harvard University, Cambridge, MA, USA., Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Genentech, Inc., South San Francisco, CA, USA., Johnson BE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. regev.aviv@gene.com.; Genentech, Inc., South San Francisco, CA, USA. regev.aviv@gene.com., Wagle N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. wagle.nikhil@gene.com.; Harvard Medical School, Boston, MA, USA. wagle.nikhil@gene.com.; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA. wagle.nikhil@gene.com.; Broad Institute of Harvard and MIT, Cambridge, MA, USA. wagle.nikhil@gene.com.; Genentech, Inc., South San Francisco, CA, USA. wagle.nikhil@gene.com.
Jazyk:	angličtina
Zdroj:	Nature medicine [Nat Med] 2024 Nov; Vol. 30 (11), pp. 3236-3249. Date of Electronic Publication: 2024 Oct 30.
DOI:	10.1038/s41591-024-03215-z
Abstrakt:	Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used them to assess variability in cell type composition and expression as well as emerging spatial expression characteristics across clinicopathological and methodological diversity. Finally, we assessed spatial expression and co-localization features of macrophage populations, characterized three distinct spatial phenotypes of epithelial-to-mesenchymal transition and identified expression programs associated with local T cell infiltration versus exclusion, showcasing the potential of clinically relevant discovery in such maps. Competing Interests: Competing interests A. Regev, J.K. and D.L.A. are co-inventors on patent application number 17/156,392, filed by the Broad Institute, for inventions relating to work in this manuscript. A. Regev is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas and, until 31 July 2020, a scientific advisory board (SAB) member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov. From 1 August 2020, A. Regev is an employee of Genentech and has equity in Roche. A. Rotem is an employee of AstraZeneca since September 2020 and has equity in AstraZeneca. E.S.B. co-founded a company that is exploring commercial applications of expansion microscopy. G.N. holds equity in and consults for Akoya Biosciences. J.G.T.Z. owns stocks in the biotechnology exchange-traded funds CNCR, IDNA, IBB and XBI, owns stock in Novo Nordisk and owns stock in Adaptive Biotechnologies, 2seventy bio and bluebird bio. J.J-V. is a contractor at Genentech since 2021. M.S. is a contractor at Genentech since November 2020. O.R.-R. is a co-inventor on patent applications filed by the Broad Institute for inventions related to single-cell genomics. She has given numerous lectures on the subject of single-cell genomics to a wide variety of audiences and, in some cases, has received remuneration to cover time and costs. O.R.-R. is an employee of Genentech since 19 October 2020 and has equity in Roche. S.J.R. is a member of the SAB of Immunitas Therapeutics and receives research funding from Bristol Myers Squibb and Kite/Gilead. X.Z. is a co-founder of and consultant for Vizgen. The other authors declare no competing interests. (© 2024. The Author(s).)
Databáze:	MEDLINE
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