Evidence map›Paper›PMID 39349005›Full record

ArticleGut2025

Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma.

Henrike Salié, Lara Wischer, Antonio D'Alessio, Ira Godbole, Yuan Suo, Patricia Otto-Mora, Juergen Beck, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher and 10 more

Abstract read
In one paragraph

Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

  1. Trial
  2. Macrophage-CD8medRxiv : the preprint server for health sciences · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
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  10. Review
  11. 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
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Improving surgical treatments for hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  18. Article
  19. Article
  20. Article
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

20 authors.

Henrike SaliéDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-2993-3782
Lara WischerDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Antonio D'AlessioDepartment of Surgery & Cancer, Imperial College London, London, UK.
Ira GodboleDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Yuan SuoDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Patricia Otto-MoraDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Juergen BeckDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Olaf NeumannInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Albrecht StenzingerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Claudia A M FulgenziDepartment of Surgery & Cancer, Imperial College London, London, UK.
Andreas BlaumeiserInstitute of Medical Bioinformatics and Systems Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Melanie BoerriesInstitute of Medical Bioinformatics and Systems Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Natascha RoehlenDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Michael SchultheißDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.
Maike HofmannDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-8410-8833
Robert ThimmeDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-1417-4135
David J PinatoDepartment of Surgery & Cancer, Imperial College London, London, UK.
Thomas LongerichInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8888-1030
Bertram BengschDepartment of Internal Medicine II, Medical Center - University of Freiburg, Freiburg, Germany bertram.bengsch@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0003-2552-740X

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundThe determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.

objectiveWe hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.

designWe conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.

resultsBioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.

Indexed as

Carcinoma, HepatocellularImmune Checkpoint InhibitorsLiver NeoplasmsAgedCD8-Positive T-LymphocytesFemaleHumansImmunotherapyMaleMiddle AgedSingle-Cell AnalysisTumor MicroenvironmentImmune Checkpoint InhibitorsCANCER IMMUNOBIOLOGYHEPATOCELLULAR CARCINOMAIMAGE ANALYSISIMMUNOTHERAPYLIVER IMMUNOLOGY

Identifiers

PMID39349005
PMCPMC11874287

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.