Evidence map›Paper›PMID 30550791›Full record

ArticleCell2018

Organoid Modeling of the Tumor Immune Microenvironment.

James T Neal, Xingnan Li, Junjie Zhu, Valeria Giangarra, Caitlin L Grzeskowiak, Jihang Ju, Iris H Liu, Shin-Heng Chiou, Ameen A Salahudeen, Amber R Smith and 24 more

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

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 993 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
993citing papers in PubMed, 5 pooled it
44.3field-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

993 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,404 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. A Tissue Explant Model for Colon Cancer.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
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  8. Review
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  16. The emerging roles of disulfidptosis in cancer.Apoptosis : an international journal on programmed cell death · 2026
    Review
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  18. Review
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  20. Review

933 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 4 institutions in 1 country.

James T NealDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Xingnan LiDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Junjie ZhuDepartment of Electrical Engineering, Stanford University School of Engineering, Stanford, CA, USA.
Valeria Giangarra10x Genomics, Pleasanton, CA, USA.
Caitlin L GrzeskowiakDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Jihang JuDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Iris H LiuDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Shin-Heng ChiouInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Ameen A SalahudeenDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Amber R SmithDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Brian C DeutschDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Lillian LiaoDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Allison J ZemekDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Fan ZhaoInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Kasper KarlssonDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Liora M SchultzDepartment of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Thomas J MetznerDepartment of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Lincoln D NadauldDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Yuen-Yi TsengBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Sahar AlkhairyBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Coyin OhBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Paula KeskulaBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Daniel Mendoza-VillanuevaTOMA Biosciences, Foster City, CA, USA.
Francisco M De La VegaTOMA Biosciences, Foster City, CA, USA.
Pamela L KunzDepartment of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Joseph C LiaoDepartment of Urology, Stanford University School of Medicine, Stanford, CA, USA.
John T LeppertDepartment of Urology, Stanford University School of Medicine, Stanford, CA, USA.
John B SunwooDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Chiara SabattiDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA; Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA.
Jesse S BoehmBroad Institute of Harvard and MIT, Cambridge, MA, USA.
William C HahnBroad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Grace X Y Zheng10x Genomics, Pleasanton, CA, USA.
Mark M DavisInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Calvin J KuoDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cjkuo@stanford.edu.
Stanford University · USBroad Institute · USHoward Hughes Medical Institute · USStanford Medicine · 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
Stanford/UNC Biomimetic U19 Research CenterU19AI116484 · NIAID · STANFORD UNIVERSITY · PI AMIEVA, MANUEL R, KUO, CALVIN J · 2015 to 2025
$13.5M
UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALVIN J KUO · 2017 to 2026
$12.9M
The Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8M
Regulation of actively proliferating and quiescent intestinal stem cellsU01DK085527 · NIDDK · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2009 to 2023
$6.9M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
T32 Training Program in Mechanisms and Innovation in Vascular DiseaseT32HL098049 · NHLBI · STANFORD UNIVERSITY · PI Nicholas James Leeper, Philip S Tsao · 2010 to 2026
$6.3M
Organoid-based Discovery of Oncogenic Drivers and Treatment Resistance MechanismsU01CA217851 · NCI · STANFORD UNIVERSITY · PI CURTIS, CHRISTINA N, JI, HANLEE P · 2017 to 2021
$4.7M
Modeling KRAS-Dependent Synthetic Lethality in Human Colon OrganoidsU01CA199241 · NCI · STANFORD UNIVERSITY · PI KUO, CALVIN J, SHOKAT, KEVAN M. · 2016 to 2019
$4.3M
Identification of Cooperative Genetic Alterations in the Pathogenesis of Oral CancerU01DE025188 · NIDCR · STANFORD UNIVERSITY · PI GEVAERT, OLIVIER, KUO, CALVIN J · 2015 to 2018
$3.8M
Functional Analysis of Oncogenic Networks in Primary OrganoidsU01CA176299 · NCI · STANFORD UNIVERSITY · PI JI, HANLEE P, KUO, CALVIN J · 2013 to 2016
$3.6M
Immunotherapy Modeling in Organoids Co-preserving Tumor and Infiltrating Immune CompartmentsR01CA251514 · NCI · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2021 to 2025
$3.2M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA244550NCI NIH HHS R01 CA251514NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA176299NCI NIH HHS U01 CA199241NCI NIH HHS U01 CA217851NCI NIH HHS U54 CA224081NHLBI NIH HHS T32 HL098049NHLBI NIH HHS T32 HL120824NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI116484NIDCR NIH HHS U01 DE025188NIDDK NIH HHS U01 DK085527NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U24 DK085532
6 · The paper itself

Abstract

In vitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.

Indexed as

Models, ImmunologicalAnimalsB7-H1 AntigenCoculture TechniquesFemaleHumansImmunotherapyMaleMiceMice, Inbred BALB CNeoplasm ProteinsNeoplasms, ExperimentalOrganoidsReceptors, Antigen, T-CellTumor MicroenvironmentB7-H1 AntigenCD274 protein, humanNeoplasm ProteinsReceptors, Antigen, T-Cellcancercheckpoint inhibitorimmunotherapyorganoidPD-1PDOsingle-cell RNA-seqT cell receptorTCRtumor-infiltrating lymphocyte

Identifiers

PMID30550791
PMCPMC6656687
OpenAlexW2905447079

What OpenQuestion holds

Textmetadata
LicenceTDM
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.