Evidence map›Paper›PMID 40760842›Full record

ArticleEuropean journal of immunology2025

CD8 T Cell Hyperfunction and Reduced Tumour Control in Murine Models of Advanced Liver Disease.

Jood Madani, Jiafeng Li, Ma Enrica Angela Ching, Agatha Vranjkovic, Katrina Jorritsma, Mohamed S Hasim, Manijeh Daneshmand, Natasha Campeau, David A Lawton, Salman Bagheri and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Jood MadaniDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Jiafeng LiDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Ma Enrica Angela ChingDepartment of Biology and Institute of Biochemistry, Carleton University, Ottawa, Canada.ORCID 0000-0002-8458-8440
Agatha VranjkovicInflammation and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Katrina JorritsmaDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Mohamed S HasimDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0000-0002-0275-3378
Manijeh DaneshmandDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Natasha CampeauDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
David A LawtonDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Salman BagheriInflammation and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Angela C CheungDivision of Gastroenterology, The Ottawa Hospital, Ottawa, Canada.
Erin E MulvihillDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Jennifer E BruinDepartment of Biology and Institute of Biochemistry, Carleton University, Ottawa, Canada.
Michele ArdolinoDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0000-0003-4114-0985
Angela M CrawleyDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0000-0002-7453-7922

Funding

Canadian Network on Hepatitis C NHC-142832CIHR PJT-419982National Sciences and Engineering Research Council of Canada RGPIN-2017-06265
6 · The paper itself

Abstract

Immune dysfunction in liver disease contributes to significant morbidities, depending on liver damage severity and aetiology. We previously reported long-lasting generalized CD8 T cell hyperfunction in chronic HCV infection with advanced fibrosis, yet its separation from viral and fibrosis-driven effects, as well as clinical outcomes of advanced fibrosis, remains unclear. In a murine model of carbon tetrachloride-induced progressive liver fibrosis, advanced fibrosis was observed by 12 weeks, with pathologies similar to those of human chronic HCV infection. Blood-circulating CD8 T cells showed IFN-γ and granzyme B (GrB) hyperfunction in response to anti-CD3/28 stimulation, as well as impaired responses to ectopic tumour challenge and anti-PD-1/CTLA-4 immunotherapy. Hyperfunction and impaired tumour responses were retained despite liver insult cessation. In a 45% HFD model, which induced steatosis and minimal fibrosis, IFN-γ and GrB hyperfunction was also observed in blood-circulating CD8 T cells. This study highlights a prolonged systemic CD8 T cell dysfunction acquired during progressive liver disease, associated with impaired antitumour and immunotherapy responses. These mirror the bulk CD8 T cell dysfunction observed in advanced liver diseases in humans, suggesting that these models could be valuable for future mechanistic studies aimed at identifying targets to help improve clinical outcomes in chronic liver disease.

Indexed as

CD8-Positive T-LymphocytesLiver CirrhosisAnimalsDisease Models, AnimalGranzymesHumansInterferon-gammaMaleMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorGranzymesGzmb protein, mouseInterferon-gammaProgrammed Cell Death 1 ReceptorCD8 T cellsimmunotherapyliver fibrosissteatosistumour response

Identifiers

PMID40760842
PMCPMC12322517

What Socratic holds

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LicenceCC BY
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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.