Evidence map›Paper›PMID 37729872›Full record

ArticleCell reports. Medicine2023

Spatially aware deep learning reveals tumor heterogeneity patterns that encode distinct kidney cancer states.

Jackson Nyman, Thomas Denize, Ziad Bakouny, Chris Labaki, Breanna M Titchen, Kevin Bi, Surya Narayanan Hari, Jacob Rosenthal, Nicita Mehta, Bowen Jiang and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% of its field
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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

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  9. Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Jackson NymanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Graduate Program in Systems Biology, Cambridge, MA, USA; Broad Institute, Cambridge, MA, USA.
Thomas DenizeDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Ziad BakounyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Chris LabakiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Breanna M TitchenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Graduate Program in Biological and Biomedical Sciences, Boston, MA, USA.
Kevin BiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA.
Surya Narayanan HariDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA.
Jacob RosenthalDepartment of Informatics & Analytics, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Nicita MehtaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Bowen JiangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Stanford University, Stanford, CA, USA.
Bijaya SharmaImmunoProfile, Department of Pathology, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
Kristen FeltImmunoProfile, Department of Pathology, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
Renato UmetonDepartment of Informatics & Analytics, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
David A BraunCenter of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Scott RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
Sabina SignorettiBroad Institute, Cambridge, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: eliezerm_vanallen@dfci.harvard.edu.
Broad Institute · USBrigham and Women's Hospital · USCornell University · USHarvard University · USYale Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Molecular Origins and Evolution to Chemoresistance in Germ Cell TumorsR37CA222574 · NCI · DANA-FARBER CANCER INST · PI VAN ALLEN, ELIEZER M · 2018 to 2024
$3.2M
Integrative Somatic and Germline Computational Biology to Redefine Clinical Actionability in Solid TumorsR01CA227388 · NCI · DANA-FARBER CANCER INST · PI VAN ALLEN, ELIEZER M · 2018 to 2022
$2.0M
Unraveling the influence of genetic subtype on spatial configurations of tissue and immune compartment composition in clear cell renal cell carcinomaF31CA250136 · NCI · HARVARD UNIVERSITY · PI NYMAN, JACKSON · 2020 to 2022
$97k
NCI NIH HHS F31 CA250136NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016359NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA227388NCI NIH HHS R37 CA222574NCI NIH HHS T32 CA009172NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is molecularly heterogeneous, immune infiltrated, and selectively sensitive to immune checkpoint inhibition (ICI). However, the joint tumor-immune states that mediate ICI response remain elusive. We develop spatially aware deep-learning models of tumor and immune features to learn representations of ccRCC tumors using diagnostic whole-slide images (WSIs) in untreated and treated contexts (n = 1,102 patients). We identify patterns of grade heterogeneity in WSIs not achievable through human pathologist analysis, and these graph-based "microheterogeneity" structures associate with PBRM1 loss of function and with patient outcomes. Joint analysis of tumor phenotypes and immune infiltration identifies a subpopulation of highly infiltrated, microheterogeneous tumors responsive to ICI. In paired multiplex immunofluorescence images of ccRCC, microheterogeneity associates with greater PD1 activation in CD8

Indexed as

CarcinomaCarcinoma, Renal CellDeep LearningKidney NeoplasmsHumansPhenotypeAIartificial intelligencecomputational histopathologycomputer visiondeep learningimmunotherapykidney cancerprecision medicinetumor heterogeneity

Identifiers

PMID37729872
PMCPMC10518628
OpenAlexW4386858415

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.