Evidence map›Paper›PMID 41023436›Full record

ArticleNature methods2025

Highly multiplexed 3D profiling of cell states and immune niches in human tumors.

Clarence Yapp, Ajit J Nirmal, Felix Zhou, Alex Y H Wong, Juliann B Tefft, Yi Daniel Lu, Zhiguo Shang, Zoltan Maliga, Paula Montero Llopis, George F Murphy and 4 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–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

35 citing papers in PubMed.

  1. Article
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  4. Review
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  8. Review
  9. Assessing the Effects of a 3-Dimensional (3D) Pathology Tissue-Processing Workflow on Downstream Molecular Analyses.Laboratory investigation; a journal of technical methods and pathology · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Fault-tolerant 3D reconstruction from 2D spatial proteomics sections.bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Review
  17. Review
  18. Article
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  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Clarence Yapp *Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1144-5710
Ajit J Nirmal *Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4139-0618
Felix ZhouLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-4463-1165
Alex Y H WongLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9315-4145
Juliann B TefftLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8826-665X
Yi Daniel LuLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0003-1740-161X
Zhiguo ShangLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-7600-7554
Zoltan MaligaLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4209-7253
Paula Montero LlopisMicroscopy Resources on the North Quad, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5983-2296
George F MurphyDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9362-5146
Christine G LianDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gaudenz DanuserLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-8583-2014
Sandro SantagataLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7528-9668
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA. peter_sorger@hms.harvard.edu.ORCID http://orcid.org/0000-0002-3364-1838

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
Technical Development Unit 2: Intelligent Hyperspectral Imaging of Subcellular Molecular States at the Whole Organ LevelU54CA268072 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI JAMES F AMATRUDA · 2021 to 2026
$9.1M
High dimensional digital pathology to investigate the tumor micro environment and its impact on response to therapyR50CA252138 · NCI · HARVARD MEDICAL SCHOOL · PI MALIGA, ZOLTAN · 2020 to 2024
$1.0M
Integrative Prediction of Therapeutic Response in T-cell Lymphoma by Omic and Spatial ModelingR00CA256497 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI NIRMAL, AJIT JOHNSON · 2023 to 2025
$747k
NCI NIH HHS P30 CA006516NCI NIH HHS R00 CA256497NCI NIH HHS R50 CA252138NCI NIH HHS U54 CA268072U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R00-CA256497U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R50-CA252138U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54-CA268072
6 · The paper itself

Abstract

Diseases such as cancer involve alterations in cell proportions, states and interactions, as well as complex changes in tissue morphology and architecture. Histopathological diagnosis of disease and most multiplexed spatial profiling relies on inspecting thin (4-5 µm) specimens. Here we describe a high-plex cyclic immunofluorescence method for three-dimensional tissue imaging and use it to show that few, if any, cells are intact in conventional thin tissue sections, reducing the accuracy of cell phenotyping and interaction analysis. However, three-dimensional cyclic immunofluorescence of sections eightfold to tenfold thicker enables accurate morphological assessment of diverse protein markers in intact tumor, immune and stromal cells. Moreover, the high resolution of this confocal approach generates images of cells in a preserved tissue environment at a level of detail previously limited to cell culture. Precise imaging of cell membranes also makes it possible to detect and map cell-cell contacts and juxtracrine signaling complexes in immune cell niches.

Indexed as

Fluorescent Antibody TechniqueImaging, Three-DimensionalNeoplasmsHumansMicroscopy, ConfocalTumor Microenvironment

Identifiers

PMID41023436
PMCPMC12510885

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Registered trials

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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.