Evidence map›Paper›PMID 41366520›Full record

ArticleEMBO molecular medicine2026

Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression.

Suresh Chava, Suresh Bugide, Parmanand Malvi, Kelly D DeMarco, Boyang Ma, Chaitanya N Parikh, Marcus Ruscetti, Allan Zajac, Guoping Cai, Romi Gupta and 1 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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.

Suresh ChavaDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0002-9360-5249
Suresh BugideDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0003-1448-1098
Parmanand MalviDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0003-4101-5025
Kelly D DeMarcoDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Boyang MaDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Chaitanya N ParikhDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Marcus RuscettiDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-4394-2087
Allan ZajacDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0001-9806-3277
Guoping CaiDepartment of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Romi GuptaDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. romigup@uab.edu.ORCID 0000-0001-5108-5962
Narendra WajapeyeeDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. nwajapey@uab.edu.ORCID 0000-0003-3306-349X

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
Deciphering and targeting a non-genetic driver pathway in hepatocellular carcinomaR01CA257046 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WAJAPEYEE, NARENDRA · 2021 to 2025
$2.3M
Role of EZH2 as a Driver and Therapeutic Target of Hepatocellular CarcinomaR01CA271613 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MICHELLE ALICE KELLIHER, Narendra Wajapeyee · 2023 to 2026
$1.8M
Senescence-Associated Secretory Phenotype (SASP) modulation of the tumor microenvironment as a therapeutic strategy for KRAS-driven tumorsR00CA241110 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RUSCETTI, MARCUS A. · 2020 to 2022
$747k
Quantifying replication dynamics to predict clonal evolution and drug sensitivity in cancer cells using single-cell whole genome sequencingF31CA271673 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI WEINER, ADAM CLAYTON · 2023 to 2024
$77k
DOD | Department of Defense Education Activity (DoDEA) HT9425-24-1-0593HHS | National Institutes of Health (NIH) R00CA241110HHS | National Institutes of Health (NIH) R01CA271673NCI NIH HHS F31 CA271673NCI NIH HHS P30 CA013148NCI NIH HHS R00 CA241110NCI NIH HHS R01 CA257046NCI NIH HHS R01 CA271613
6 · The paper itself

Abstract

Natural Killer (NK) cells play a critical role in regulating tumor growth, but our understanding of the mechanisms underlying their anti-tumor activity remains limited. We identified the histone methyltransferase EHMT2 as a key suppressor of NK cell-mediated cytotoxicity. EHMT2 inhibition in cancer cells enhanced NK cell-mediated elimination of diverse cancers, including uveal melanoma, breast cancer, and pancreatic cancer. EHMT2 loss increased AZGP1 and decreased TGF-β1 levels, resulting in the autocrine elevation of NKG2D ligands MICB and ULBP3, chemokines in cancer cells, and the paracrine stimulation of NK cell function. In a syngeneic pancreatic cancer model, EHMT2 inhibition suppressed tumors in an NK cell-dependent manner, as NK cell depletion restored tumor growth. This effect persisted and remained dependent on NK cells in Rag2 knockout mice (lacking T and B cells), but not in NSG mice (lacking T-, B- and NK-cells). Furthermore, EHMT2 and TGF-β1 inhibitors suppressed tumors in immunocompetent, but not in immunodeficient mice. These findings establish EHMT2 as a suppressor of NK cell-mediated anti-tumor immunity and a promising therapeutic target.

Indexed as

Histone-Lysine N-MethyltransferaseKiller Cells, NaturalNeoplasmsTransforming Growth Factor beta1AnimalsCell Line, TumorDisease Models, AnimalHistocompatibility AntigensHumansMiceMice, KnockoutEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseTransforming Growth Factor beta1Anti-tumor immunityAZGP1EHMT2NK CellsTGF-β1

Identifiers

PMID41366520
PMCPMC12808752

What Socratic holds

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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 Socratic graph.