Evidence map›Paper›PMID 34593621›Full record

ArticleJournal for immunotherapy of cancer2021

Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

David J Pinato, Sam M Murray, Alejandro Forner, Takahiro Kaneko, Petros Fessas, Pierluigi Toniutto, Beatriz Mínguez, Valentina Cacciato, Claudio Avellini, Alba Diaz and 11 more

3 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 161 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed, 9 pooled it
10.8field-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.

NCT05278195 unknown statusnot on this mapstarted 2022, after this paper: background citation

Assessing the Prognosis of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Hepatocellular Carcinoma by Using Clinical and Imaging Biomarkers

TypeobservationalSponsorZhongda HospitalRan2022 to 2023Enrolled300ConditionsHepatocellular Carcinoma
NCT05332496 completednot on this mapstarted 2022, after this paper: background citation

Efficacy and Safety of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Intermediate Stage HCC

Typeobservational_patient_registrySponsorZhongda HospitalRan2022 to 2025Enrolled941ConditionsHepatocellular CarcinomaArmsPD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab, TACE
NCT05332821 completednot on this mapstarted 2022, after this paper: background citation

Efficacy and Safety of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Advanced Stage HCC

Typeobservational_patient_registrySponsorZhongda HospitalRan2022 to 2024Enrolled1,244ConditionsHepatocellular CarcinomaArmsPD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab, TACE
3 · Its place in the literature

Who cites it

161 citing papers in PubMed, 9 syntheses or guidelines pooled it, 188 citations in OpenAlex.

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101 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

21 authors at 12 institutions in 4 countries.

David J PinatoDepartment of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK david.pinato@imperial.ac.uk.ORCID 0000-0002-3529-0103
Sam M MurrayDepartment of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Alejandro FornerLiver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, University of Barcelona, Hospital Clinic, Barcelona, Spain.
Takahiro KanekoTokyo Medical and Dental University, Bunkyo-ku, Japan.
Petros FessasDepartment of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.ORCID 0000-0002-7472-8913
Pierluigi ToniuttoHepatology and Liver Transplantation Unit, Department of Medical Area (DAME), University of Udine, Udine, Italy.
Beatriz MínguezLiver Unit, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
Valentina CacciatoGastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy.
Claudio AvelliniInstitute of Histopathology, Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia", Udine, Italy.
Alba DiazPathology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Rosemary J BoytonDepartment of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Daniel M AltmannDepartment of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Robert D GoldinCentre for Pathology, Imperial College London, London, UK.
Ayse U AkarcaDepartment of Histopathology, University College London Cancer Institute, London, UK.
Teresa MarafiotiDepartment of Histopathology, University College London Cancer Institute, London, UK.
Francesco A MauriDepartment of Surgery and Cancer, Imperial College London, London, UK.
Edoardo CasagrandeGastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy.
Federica GrilloDepartment of Surgical Sciences, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy.
Edoardo GianniniGastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy.
Sherrie BhooriDepartment of Oncology, University of Milan, Milano, Italy.
Vincenzo MazzaferroDepartment of Oncology, University of Milan, Milano, Italy.
Hammersmith Hospital · GBOspedale Policlinico San Martino · ITImperial College London · GBLondon Cancer · GBUniversity of Milan · ITInstituto de Salud Carlos III · ESOspedale Santa Maria della Misericordia di Udine · ITTokyo Medical and Dental University · JPUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversitat Autònoma de Barcelona · ESUniversitat de Barcelona · ESUniversity of Udine · IT

Funding

Cancer Research UK 26137Cancer Research UK C57701/A26137Wellcome TrustWellcome Trust PS3416
6 · The paper itself

Abstract

backgroundModulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.

methodsWe profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163.

resultsWe analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-.

conclusionsTACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.

Indexed as

AdultAgedCarcinoma, HepatocellularChemoembolization, TherapeuticFemaleHumansImmunogenic Cell DeathImmunotherapyLiver NeoplasmsMaleMiddle Agedimmunotherapyliver neoplasms

Identifiers

PMID34593621
PMCPMC8487214
OpenAlexW3199675843

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.