Evidence map›Paper›PMID 36108710›Full record

ArticleGastroenterology2023

Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

Philipp K Haber, Florian Castet, Miguel Torres-Martin, Carmen Andreu-Oller, Marc Puigvehí, Maeda Miho, Pompilia Radu, Jean-Francois Dufour, Chris Verslype, Carolin Zimpel and 25 more

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

Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
18.7field-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

100 citing papers in PubMed, 138 citations in OpenAlex.

  1. Review
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  3. From Theory to Practice: Which Biomarkers Are Ready for Predicting Response in Advanced HCC?Liver international : official journal of the International Association for the Study of the Liver · 2026
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40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 15 institutions in 7 countries.

Philipp K HaberMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Surgery, Campus Charité Mitte and Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
Florian CastetTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain.
Miguel Torres-MartinTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain.
Carmen Andreu-OllerMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Marc PuigvehíMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Hepatology Section, Gastroenterology Department, Parc de Salut Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.
Maeda MihoMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Pompilia RaduUniversity Clinic for Visceral Surgery and Medicine, University of Bern, Inselspital, Bern, Switzerland.
Jean-Francois DufourUniversity Clinic for Visceral Surgery and Medicine, University of Bern, Inselspital, Bern, Switzerland; Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland.
Chris VerslypeDepartment of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium.
Carolin ZimpelDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany; Department of Medicine I, University of Lübeck, UKSH - Campus Lübeck, Lübeck, Germany.
Jens U MarquardtDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany; Department of Medicine I, University of Lübeck, UKSH - Campus Lübeck, Lübeck, Germany.
Peter R GalleDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany.
Arndt VogelDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Melanie BathonDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Tim MeyerDepartment of Oncology, University College London Cancer Institute, London, United Kingdom.
Ismail LabgaaDepartment of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Antonia DigkliaDepartment of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Lewis R RobertsDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Mohamed A Mohamed AliDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Beatriz MínguezLiver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain, Liver Diseases Research Group, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain, CIBERehd, Universitat Autònoma de Barcelona, Barcelona, Spain.
Davide CitterioGastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Department of Oncology, University of Milan, Milan, Italy.
Vincenzo MazzaferroGastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Department of Oncology, University of Milan, Milan, Italy.
Fabian FinkelmeierDepartment of Gastroenterology, University Liver and Cancer Centre, Frankfurt, Germany.
Jörg TrojanDepartment of Gastroenterology, University Liver and Cancer Centre, Frankfurt, Germany.
Burcin ÖzdirikDepartment of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité University Medicine Berlin, Berlin, Germany.
Tobias MüllerDepartment of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité University Medicine Berlin, Berlin, Germany.
Moritz SchmelzleDepartment of Surgery, Campus Charité Mitte and Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
Anthony BejjaniDivision of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, California.
Max W SungMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Myron E SchwartzMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Richard S FinnDivision of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, California.
Swan ThungMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Augusto VillanuevaMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Daniela SiaMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Josep M LlovetMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. Electronic address: josep.llovet@mssm.edu.
Icahn School of Medicine at Mount Sinai · USJohannes Gutenberg University Mainz · DEMedizinische Hochschule Hannover · DECharité - Universitätsmedizin Berlin · DEConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESMayo Clinic · USUniversitat Autònoma de Barcelona · ESUniversity of Bern · CHUniversity of California, Los Angeles · USUniversity of Lausanne · CHUniversity of Milan · ITHumboldt-Universität zu Berlin · DEInstitució Catalana de Recerca i Estudis Avançats · ESKU Leuven · BELondon Cancer · GB

Funding

THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deanna L Benson · 2015 to 2026
$35.4M
Project 4: ImmunovirotherapyP50CA210964 · NCI · MAYO CLINIC ROCHESTER · PI Rory Smoot · 2018 to 2026
$20.5M
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
Cancer Research UK 26813Cancer Research UK C9380/A26813Department of HealthNCI NIH HHS P30 CA196521NCI NIH HHS P50 CA210964NIDDK NIH HHS R01 DK128289
6 · The paper itself

Abstract

BACKGROUND &

aimsSingle-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1.

methodsOverall, 111 tumor samples from patients with aHCC were obtained from 13 centers before systemic therapies. We performed molecular analysis and immune deconvolution using whole-genome expression data (n = 83), mutational analysis (n = 72), and histologic evaluation with an endpoint of objective response.

resultsAmong 83 patients with transcriptomic data, 28 were treated in frontline, whereas 55 patients were treated after tyrosine kinase inhibitors (TKI) either in second or third line. Responders treated in frontline showed upregulated interferon-γ signaling and major histocompatibility complex II-related antigen presentation. We generated an 11-gene signature (IFNAP), capturing these molecular features, which predicts response and survival in patients treated with anti-PD1 in frontline. The signature was validated in a separate cohort of aHCC and >240 patients with other solid cancer types where it also predicted response and survival. Of note, the same signature was unable to predict response in archival tissue of patients treated with frontline TKIs, highlighting the need for fresh biopsies before immunotherapy.

conclusionInterferon signaling and major histocompatibility complex-related genes are key molecular features of HCCs responding to anti-PD1. A novel 11-gene signature predicts response in frontline aHCC, but not in patients pretreated with TKIs. These results must be confirmed in prospective studies and highlights the need for biopsies before immunotherapy to identify biomarkers of response.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsBiomarkersHumansProgrammed Cell Death 1 ReceptorProspective StudiesBiomarkersProgrammed Cell Death 1 ReceptorBiomarkersHepatocellular CarcinomaImmunotherapyPredictors of Response

Identifiers

PMID36108710
PMCPMC12182972
OpenAlexW4295677793

What OpenQuestion holds

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Registered trials

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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.