Evidence map›Paper›PMID 34019793›Full record

ArticleCell2021

Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages.

Aleksandar Obradovic, Nivedita Chowdhury, Scott M Haake, Casey Ager, Vinson Wang, Lukas Vlahos, Xinzheng V Guo, David H Aggen, W Kimryn Rathmell, Eric Jonasch and 7 more

Abstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers.

0numbers the graph read from it
0cells of the map it votes in
235citing 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

235 citing papers in PubMed.

  1. Trial
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  10. Identification of a distinct cluster of LY6EBritish journal of cancer · 2026
    Article
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  13. FN1Oncogene · 2026
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175 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Aleksandar ObradovicColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA; Department of Systems Biology, HICC, New York, NY 10032, USA.
Nivedita ChowdhuryColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Scott M HaakeMD Anderson Cancer Center, Houston, TX, USA.
Casey AgerColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA.
Vinson WangDepartment of Urology, Herbert Irving Comprehensive Cancer Center (HICC), New York, NY 10032, USA.
Lukas VlahosDepartment of Systems Biology, HICC, New York, NY 10032, USA.
Xinzheng V GuoColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA.
David H AggenColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA.
W Kimryn RathmellVanderbilt University Medical Center, Nashville, TN, USA.
Eric JonaschVanderbilt University Medical Center, Nashville, TN, USA.
Joyce E JohnsonVanderbilt University Medical Center, Nashville, TN, USA.
Marc RothVanderbilt University Medical Center, Nashville, TN, USA.
Kathryn E BeckermannVanderbilt University Medical Center, Nashville, TN, USA.
Brian I RiniVanderbilt University Medical Center, Nashville, TN, USA.
James McKiernanDepartment of Urology, Herbert Irving Comprehensive Cancer Center (HICC), New York, NY 10032, USA; HICC, Columbia University, New York, NY, USA.
Andrea CalifanoDepartment of Systems Biology, HICC, New York, NY 10032, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; HICC, Columbia University, New York, NY, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY; Department of Biomedical Informatics, Columbia University, New York, NY, USA; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA; J.P. Sulzberger Columbia Genome Center, New York, NY, USA. Electronic address: ac2248@cumc.columbia.edu.
Charles G DrakeColumbia Center for Translational Immunology (CCTI), Columbia University Irving Medical Center (CUMC), New York, NY 10032, USA; Department of Urology, Herbert Irving Comprehensive Cancer Center (HICC), New York, NY 10032, USA; HICC, Columbia University, New York, NY, USA. Electronic address: cgd2139@columbia.edu.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Parisa Tehranifar · 1985 to 2026
$115.3M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Systematic Identification and Pharmacological Targeting of Tumor Dependencies for Precision Cancer MedicineU01CA217858 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2017 to 2021
$6.1M
Metabolic Barriers to T Cell Activation in Clear Cell Renal Cell CarcinomaR01CA217987 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey C Rathmell · 2018 to 2026
$4.3M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
Analysis of Lag-3 in Regulatory T Cell Function and Immune SupressionR01CA127153 · NCI · JOHNS HOPKINS UNIVERSITY · PI DRAKE, CHARLES G. · 2008 to 2012
$1.7M
CAPRI: Columbia Cancer Training Program for Resident-InvestigatorsR38CA231577 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CREW, KATHERINE D, SCHWARTZ, GARY K · 2018 to 2021
$1.4M
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
Discovering Network-Based Drivers of Single-Cell Transcriptional State in Tumor Immune Microenvironment to Reveal Immuno-Therapeutic Targets and Treatment SynergiesF30CA260765 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OBRADOVIC, ALEKSANDAR ZORAN · 2021 to 2022
$98k
NCI NIH HHS F30 CA260765NCI NIH HHS K12 CA090625NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA013696NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA127153NCI NIH HHS R01 CA217987NCI NIH HHS R35 CA197745NCI NIH HHS R38 CA231577NCI NIH HHS U01 CA217858NIH HHS S10 OD012351NIH HHS S10 OD021764
6 · The paper itself

Abstract

Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target.

Indexed as

AdultApolipoproteins EBiomarkers, TumorCarcinoma, Renal CellCohort StudiesFemaleGene ExpressionGene Expression Regulation, NeoplasticHumansKidneyKidney NeoplasmsLymphocytes, Tumor-InfiltratingMacrophagesMaleMembrane GlycoproteinsMiddle AgedApoE protein, humanApolipoproteins EBiomarkers, Tumorcomplement 1q receptorMembrane GlycoproteinsReceptors, ComplementReceptors, ImmunologicTREM2 protein, humanCD8 T cellclear cell renal carcinomaclusteringgene regulatory networksimmunotherapypost-surgical recurrenceprotein activity inferencesingle-cell RNA sequencingTregtumor-infiltrating macrophagetumor microenvironment

Identifiers

PMID34019793
PMCPMC8479759

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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.