Evidence map›Paper›PMID 39478111›Full record

ArticleNature medicine2024

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

Johanna Klughammer, Daniel L Abravanel, Åsa Segerstolpe, Timothy R Blosser, Yury Goltsev, Yi Cui, Daniel R Goodwin, Anubhav Sinha, Orr Ashenberg, Michal Slyper and 49 more

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In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  11. Target discovery and drug design in the era of artificial intelligence.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

59 authors.

Johanna Klughammer *Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. klughammer@genzentrum.lmu.de.ORCID http://orcid.org/0000-0002-3628-9278
Daniel L Abravanel *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. daniel_abravanel@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-0129-1618
Åsa Segerstolpe *Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Timothy R Blosser *Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7739-922X
Yury Goltsev *Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4079-7969
Yi CuiDepartment of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Daniel R GoodwinDepartment of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Anubhav SinhaDepartment of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Orr AshenbergKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Michal SlyperKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sébastien VigneauCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Judit Jané-ValbuenaKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Shahar AlonDepartment of Media Arts and Sciences, McGovern Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Chiara CaraccioBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3580-1348
Judy ChenCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Ofir CohenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nicole CullenCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6541-8588
Laura K DelloStrittoCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Danielle DionneKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Janet FilesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Allison FrangiehCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Karla HelvieCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Melissa E HughesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Stephanie IngaCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Abhay KanodiaCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Ana LakoCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Colin MacKichanCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Simon MagesKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1447-6811
Noa MorielSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Evan MurrayBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Sara NapolitanoCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Kyleen NguyenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mor NitzanSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID http://orcid.org/0000-0003-0074-9196
Rebecca OrtizCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Miraj PatelCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Kathleen L PfaffCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Caroline B M PorterKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Asaf RotemCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Sarah StraussDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Robert StrasserGene Center and Department of Biochemistry, Ludwig Maximilians Universität München, Munich, Germany.
Aaron R ThornerCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Madison TurnerCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Isaac WakiroCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5248-4823
Julia WaldmanKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jingyi WuCenter for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Jorge Gómez Tejeda ZañudoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1092-0068
Diane ZhangBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Nancy U LinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2263-5413
Sara M TolaneyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5940-8671
Eric P WinerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Edward S BoydenDepartment of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0419-3351
Fei ChenBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2308-3649
Garry P NolanBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Scott J RodigCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Xiaowei ZhuangDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Bruce E JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. regev.aviv@gene.com.
Nikhil WagleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. wagle.nikhil@gene.com.ORCID http://orcid.org/0000-0003-3332-9438

Funding

Tissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI Nabihah Tayob · 2013 to 2026
$30.1M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Conquer Cancer Foundation (Conquer Cancer Foundation of the American Society of Clinical Oncology) 17095Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation) 2019_A70European Molecular Biology Organization (EMBO) ALTF 738-2017Human Frontier Science Program (HFSP) LT000452/2019-LNCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS P50 CA168504NCI NIH HHS T32 CA009172U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1P50CA168504U.S. Department of Health & Human Services | National Institutes of Health (NIH) HHSN261100039 / HHSN26120150000
6 · The paper itself

Abstract

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.

Indexed as

Breast NeoplasmsEpithelial-Mesenchymal TransitionNeoplasm MetastasisSingle-Cell AnalysisTumor MicroenvironmentAdultBiopsyFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMiddle AgedSequence Analysis, RNAT-Lymphocytes

Identifiers

PMID39478111
PMCPMC11564109

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.