Evidence map›Paper›PMID 41923620›Full record

ArticleCell reports. Medicine2026

Histone methyl-transferase G9a inhibition boosts the efficacy of immune checkpoint inhibitors in experimental hepatocellular carcinoma.

Elena Adan-Villaescusa, Borja Castello-Uribe, Iker Uriarte, Eva Santamaria, Roberto Barbero, Miriam Belzunce, Amaya López-Pascual, Maria Ujue Latasa, Jasmin Elurbide, Emiliana Valbuena-Goiricelaya and 21 more

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Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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3 · Its place in the literature

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2 citing papers in PubMed.

  1. Review
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4 · The record

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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

31 authors.

Elena Adan-VillaescusaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Borja Castello-UribeHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Iker UriarteHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Eva SantamariaCIBERehd, Instituto de Salud Carlos III, Madrid, Spain; RNA Biology and Therapy Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Roberto BarberoHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Miriam BelzunceHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Amaya López-PascualHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
Maria Ujue LatasaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Jasmin ElurbideHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Emiliana Valbuena-GoiricelayaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Agavni MesropianLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Guillem Cano-SegarraLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Ana Hernández de SandeLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Lorenzo NeviMicroscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
Simone CarottiMicroscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
Umberto Vespasiani-GentilucciUnità di Epatologia, Università Campus Biomedico di Roma, Rome, Italy.
Felipe ProsperInstituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hemato-Oncology Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERonc, Instituto de Salud Carlos III, Madrid, Spain.
Antonio Pineda-LucenaMolecular Therapeutics Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Bruno SangroCIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain.
Josepmaria ArgemiCIBERehd, Instituto de Salud Carlos III, Madrid, Spain; RNA Biology and Therapy Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain.
Pedro BerraondoInstituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; CIBERonc, Instituto de Salud Carlos III, Madrid, Spain; Immunology and Immunotherapy Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Pablo SarobeCIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Immunology and Immunotherapy Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Albert Gris-OliverLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Roser PinyolLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Josep M LlovetLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalonia, Spain; Mount Sinai Liver Cancer Program (Divisions of Liver Diseases, Department of Hematology/Oncology, Department of Medicine), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
Maria ArechederraHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
Carmen BerasainHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Alexis CocozakiIpsen Biopharmaceuticals, Cambridge, MA, USA.
Veronica GibajaIpsen Biopharmaceuticals, Cambridge, MA, USA.
Matias A AvilaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
Maite G Fernandez-BarrenaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain. Electronic address: magarfer@unav.es.

Funding

The Role of KLF6 in Hepatic FibrosisR01DK056621 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FRIEDMAN, SCOTT L. · 2000 to 2019
$6.2M
Hepatic stellate cells in NASH fibrosis and HCCR01DK128289 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCOTT L. FRIEDMAN · 2021 to 2026
$2.6M
Determinants of immunotherapy response in NASH-Hepatocellular carcinomaR01CA273932 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JOSEP M LLOVET · 2023 to 2026
$2.0M
NCI NIH HHS R01 CA273932NIDDK NIH HHS R01 DK056621NIDDK NIH HHS R01 DK128289
6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICIs) transform cancer therapy, but their efficacy in hepatocellular carcinoma (HCC) remains limited due to tumor-intrinsic immune evasion. We investigate the epigenetic regulator G9a (EHMT2) as a driver of immune resistance and evaluate pharmacologic inhibition as a therapeutic strategy. G9a expression is analyzed across human HCC cohorts and correlated with transcriptomic signatures predictive of ICI response. Using human and murine HCC cell lines and immunocompetent mouse models, we assess the antitumor effects of two G9a inhibitors, CM272 and EZM8266, combined with anti-PD1 therapy. Elevated G9a expression inversely correlates with immune-related signatures of ICI responsiveness. G9a inhibition restores interferon gamma (IFN-γ) signaling, increases major histocompatibility complex (MHC) class I expression, enhances CXCL10-mediated T cell recruitment, and induces viral mimicry via derepression of endogenous retroviral elements and cytosolic double-stranded RNA (dsRNA) accumulation. In vivo, G9a inhibition synergizes with anti-PD1 therapy, suppresses tumor growth, and enhances CD8

Indexed as

Carcinoma, HepatocellularHistone-Lysine N-MethyltransferaseImmune Checkpoint InhibitorsLiver NeoplasmsAnimalsCD8-Positive T-LymphocytesCell Line, TumorGene Expression Regulation, NeoplasticHistocompatibility AntigensHumansInterferon-gammaMiceEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseImmune Checkpoint InhibitorsInterferon-gammaepidrugsepigeneticsG9ahepatocellular carcinomahistone methylationimmune checkpoint inhibitorsimmune evasion

Identifiers

PMID41923620
PMCPMC13130624

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.