Evidence map›Paper›PMID 34093591›Full record

ArticleFrontiers in immunology2021

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging.

Darci Phillips, Christian M Schürch, Michael S Khodadoust, Youn H Kim, Garry P Nolan, Sizun Jiang

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
8.8field-weighted citation impact, top 1% 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

78 citing papers in PubMed, 106 citations in OpenAlex.

  1. Trial
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  8. Spatial Multiomics Reveal Insights Into ADC Efficacy.European journal of immunology · 2026
    Review
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18 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

6 authors at 1 institution in 1 country.

Darci PhillipsDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Christian M SchürchDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Michael S KhodadoustDivision of Oncology, Stanford University School of Medicine, Stanford, CA, United States.
Youn H KimDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA, United States.
Garry P NolanDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Sizun JiangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Stanford University · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NOLAN, GARRY P · 2012 to 2021
$49.1M
Technology CoreU19AI135976 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI ADEREM, ALAN A · 2018 to 2022
$17.0M
The Cellular Geography of Therapeutic Resistance in CancerU2CCA233195 · NCI · DANA-FARBER CANCER INST · PI VAN ALLEN, ELIEZER M · 2018 to 2023
$13.7M
Project 3: Identifying plasma biomarkers predicting time to HIV rebound after treatment interruptionP01AI131374 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI GREENE, WARNER C. · 2017 to 2021
$8.5M
The Lung PCA: A Multi-Dimensional Atlas of Pulmonary PremalignancyU2CCA233238 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DUBINETT, STEVEN M., SPIRA, AVRUM E · 2018 to 2021
$7.0M
Stanford Tissue Mapping CenterU54HG010426 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2021
$5.1M
Tissue Cytokine Sequestration and Immune Regulation in AutoimmunityU01AI101984 · NIAID · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2012 to 2021
$5.0M
Postgraduate Training Program in Epithelial BiologyT32AR007422 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1986 to 2026
$5.0M
Multiscale Modeling of Myelodysplastic SyndromesR01HL128173 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI COREY, SETH JOEL, KIMMEL, MAREK · 2015 to 2019
$3.8M
Balanced signaling cues to guide cell transitions in the blood lineage continuumR01HL120724 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAKRABORTY, ARUP K., NOLAN, GARRY P · 2015 to 2019
$3.7M
T Cell Reagent Research for Monitoring T Cell in Food AllergyU01AI140498 · NIAID · STANFORD UNIVERSITY · PI NADEAU, KARI C. · 2018 to 2022
$1.8M
NCI NIH HHS F32 CA233203NCI NIH HHS F99 CA212231NCI NIH HHS R33 CA183692NCI NIH HHS U2C CA233195NCI NIH HHS U2C CA233238NHGRI NIH HHS U54 HG010426NHLBI NIH HHS R01 HL120724NHLBI NIH HHS R01 HL128173NIAID NIH HHS P01 AI131374NIAID NIH HHS U01 AI101984NIAID NIH HHS U01 AI140498NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI100627NIAID NIH HHS U19 AI135976NIAMS NIH HHS T32 AR007422NIDDK NIH HHS UG3 DK114937
6 · The paper itself

Abstract

Immunotherapies are revolutionizing cancer treatment by boosting the natural ability of the immune system. In addition to antibodies against traditional checkpoint molecules or their ligands (i.e., CTLA-4, PD-1, and PD-L1), therapies targeting molecules such as ICOS, IDO-1, LAG-3, OX40, TIM-3, and VISTA are currently in clinical trials. To better inform clinical care and the design of therapeutic combination strategies, the co-expression of immunoregulatory proteins on individual immune cells within the tumor microenvironment must be robustly characterized. Highly multiplexed tissue imaging platforms, such as CO-Detection by indEXing (CODEX), are primed to meet this need by enabling >50 markers to be simultaneously analyzed in single-cells on formalin-fixed paraffin-embedded (FFPE) tissue sections. Assembly and validation of antibody panels is particularly challenging, with respect to the specificity of antigen detection and robustness of signal over background. Herein, we report the design, development, optimization, and application of a 56-marker CODEX antibody panel to eight cutaneous T cell lymphoma (CTCL) patient samples. This panel is comprised of structural, tumor, and immune cell markers, including eight immunoregulatory proteins that are approved or currently undergoing clinical trials as immunotherapy targets. Here we provide a resource to enable extensive high-dimensional, spatially resolved characterization of the tissue microenvironment across tumor types and imaging modalities. This framework provides researchers with a readily applicable blueprint to study tumor immunology, tissue architecture, and enable mechanistic insights into immunotherapeutic targets.

Indexed as

Fluorescent Antibody TechniqueSingle-Cell AnalysisTissue Array AnalysisTumor MicroenvironmentBiomarkers, TumorClinical Decision-MakingHigh-Throughput Screening AssaysHumansImage Processing, Computer-AssistedImmune Checkpoint InhibitorsImmune Checkpoint ProteinsImmunotherapyLymphoma, T-Cell, CutaneousMicroscopy, FluorescencePredictive Value of TestsSkin NeoplasmsBiomarkers, TumorImmune Checkpoint InhibitorsImmune Checkpoint Proteinscancer immunityCODEX multiplexed tissue imagingimmunophenotypingimmunoregulatory proteinsimmunotherapylymphomatumor microenvironment

Identifiers

PMID34093591
PMCPMC8170307
OpenAlexW3162853653

What OpenQuestion holds

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LicenceCC BY
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.