Evidence map›Paper›PMID 32645139›Full record

ArticleThe Journal of cell biology2020

Cancer cells educate natural killer cells to a metastasis-promoting cell state.

Isaac S Chan, Hildur Knútsdóttir, Gayathri Ramakrishnan, Veena Padmanaban, Manisha Warrier, Juan Carlos Ramirez, Matthew Dunworth, Hao Zhang, Elizabeth M Jaffee, Joel S Bader and 1 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% 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

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  10. Tumor organoid-immune cell co-culture systems for precision oncology.Frontiers in cell and developmental biology · 2026
    Review
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  15. Biomolecules & biomedicine · 2025
    Article
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37 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

11 authors at 1 institution in 1 country.

Isaac S ChanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Hildur KnútsdóttirDepartment of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD.
Gayathri RamakrishnanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Veena PadmanabanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Manisha WarrierDepartment of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD.
Juan Carlos RamirezDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Matthew DunworthDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Hao ZhangDepartment of Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD.
Elizabeth M JaffeeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Joel S BaderDepartment of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD.
Andrew Josef EwaldDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
Pathway Discovery and Target Validation for Outgrowth of Breast Cancer MetastasesU01CA217846 · NCI · JOHNS HOPKINS UNIVERSITY · PI BADER, JOEL S., EWALD, ANDREW JOSEF · 2017 to 2021
$4.8M
Integrating bioinformatics into multiscale models for hepatocellular carcinomaU01CA212007 · NCI · JOHNS HOPKINS UNIVERSITY · PI EWALD, ANDREW JOSEF, FERTIG, ELANA · 2018 to 2022
$3.2M
NCI NIH HHS P30 CA006973NCI NIH HHS T32 CA009071NCI NIH HHS U01 CA212007NCI NIH HHS U01 CA217846
6 · The paper itself

Abstract

Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer cells escape NK cell surveillance. Using ex vivo and in vivo models of metastasis, we establish that keratin-14+ breast cancer cells are vulnerable to NK cells. We then discovered that exposure to cancer cells causes NK cells to lose their cytotoxic ability and promote metastatic outgrowth. Gene expression comparisons revealed that healthy NK cells have an active NK cell molecular phenotype, whereas tumor-exposed (teNK) cells resemble resting NK cells. Receptor-ligand analysis between teNK cells and tumor cells revealed multiple potential targets. We next showed that treatment with antibodies targeting TIGIT, antibodies targeting KLRG1, or small-molecule inhibitors of DNA methyltransferases (DMNT) each reduced colony formation. Combinations of DNMT inhibitors with anti-TIGIT or anti-KLRG1 antibodies further reduced metastatic potential. We propose that NK-directed therapies targeting these pathways would be effective in the adjuvant setting to prevent metastatic recurrence.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorFemaleHumansKiller Cells, NaturalMCF-7 CellsMethyltransferasesMiceNeoplasm MetastasisReceptors, ImmunologicMethyltransferasesReceptors, Immunologic

Identifiers

PMID32645139
PMCPMC7480097
OpenAlexW3041158987

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.