Evidence map›Paper›PMID 35477863›Full record

ArticleGut2022

CXCR2 inhibition enables NASH-HCC immunotherapy.

Jack Leslie, John B G Mackey, Thomas Jamieson, Erik Ramon-Gil, Thomas M Drake, Frédéric Fercoq, William Clark, Kathryn Gilroy, Ann Hedley, Colin Nixon and 36 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 2 pooled it
17.4field-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

138 citing papers in PubMed, 2 syntheses or guidelines pooled it, 216 citations in OpenAlex.

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78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors at 13 institutions in 10 countries.

Jack LeslieNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.ORCID http://orcid.org/0000-0001-6443-2396
John B G MackeyCancer Research UK Beatson Institute, Glasgow, UK.
Thomas JamiesonCancer Research UK Beatson Institute, Glasgow, UK.
Erik Ramon-GilNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Thomas M DrakeCancer Research UK Beatson Institute, Glasgow, UK.
Frédéric FercoqCancer Research UK Beatson Institute, Glasgow, UK.ORCID http://orcid.org/0000-0002-4825-024X
William ClarkCancer Research UK Beatson Institute, Glasgow, UK.
Kathryn GilroyCancer Research UK Beatson Institute, Glasgow, UK.
Ann HedleyCancer Research UK Beatson Institute, Glasgow, UK.
Colin NixonCancer Research UK Beatson Institute, Glasgow, UK.
Saimir LuliNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Maja LaszczewskaNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Roser PinyolTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0002-0288-6314
Roger Esteban-FabróTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Catherine E WilloughbyTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0002-0617-8833
Philipp K HaberMount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Carmen Andreu-OllerTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Mohammad RahbariDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1133-2134
Chaofan FanDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
Dominik PfisterDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
Shreya RamanDepartment of Pathology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Niall WilsonNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Miryam MüllerCancer Research UK Beatson Institute, Glasgow, UK.ORCID http://orcid.org/0000-0002-0751-1407
Amy CollinsNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Daniel GehNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.ORCID http://orcid.org/0000-0002-3592-7469
Andrew FullerFlow Cytometry Facility, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
David McDonaldFlow Cytometry Facility, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Gillian HulmeFlow Cytometry Facility, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Andrew FilbyFlow Cytometry Facility, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Xabier Cortes-LavaudCancer Research UK Beatson Institute, Glasgow, UK.
Noha-Ehssan MohamedCancer Research UK Beatson Institute, Glasgow, UK.
Catriona A FordCancer Research UK Beatson Institute, Glasgow, UK.
Ximena L Raffo IraolagoitiaCancer Research UK Beatson Institute, Glasgow, UK.
Amanda J McFarlaneCancer Research UK Beatson Institute, Glasgow, UK.
Misti V McCainThe Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
Rachel A RidgwayCancer Research UK Beatson Institute, Glasgow, UK.
Edward W RobertsCancer Research UK Beatson Institute, Glasgow, UK.
Simon T BarryBioscience, Early Oncology, AstraZeneca, Macclesfield, UK.
Gerard J GrahamChemokine Research Group, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Mathias HeikenwälderDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
Helen L ReevesThe Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
Josep M LlovetTranslational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Leo M CarlinCancer Research UK Beatson Institute, Glasgow, UK.
Thomas G BirdCancer Research UK Beatson Institute, Glasgow, UK.ORCID http://orcid.org/0000-0002-6120-1581
Owen J SansomCancer Research UK Beatson Institute, Glasgow, UK.
Derek A MannNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK derek.mann@newcastle.ac.uk.
Cancer Research UK Scotland Institute · GBUniversity of Newcastle Australia · AUBioscience (China) · CNGerman Cancer Research Center · DECancer Institute (WIA) · INInstitute of Cancer Research · CAConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESAstraZeneca (United Kingdom) · GBClinical Research Institute · USInstitució Catalana de Recerca i Estudis Avançats · ESInstitute of Infection and Immunity · CAKoç University · TRNewcastle upon Tyne Hospitals NHS Foundation Trust · GB

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
Hepatic autophagy, progenitor cells and fibrosisR56DK056621 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FRIEDMAN, SCOTT L. · 2015 to 2015
$297k
Cancer Research UK 23390Cancer Research UK 23983Cancer Research UK 26813Cancer Research UK A23983Medical Research Council MR/M01245X/1Medical Research Council MR/R023026/1NIDDK NIH HHS R01 DK056621NIDDK NIH HHS R01 DK128289NIDDK NIH HHS R56 DK056621Wellcome Trust
6 · The paper itself

Abstract

objectiveHepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy.

designNeutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry.

resultsNeutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1

conclusionCXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC.

Indexed as

hepatocellular carcinomaimmunotherapynonalcoholic steatohepatitis

Identifiers

PMID35477863
PMCPMC9484388
OpenAlexW4226052234

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.