Evidence map›Paper›PMID 42477793›Full record

ArticleMolecular cancer2026

Evidence of endothelial anergy and T-cell exclusion in microsatellite stable colorectal liver metastases revealed through human hemi-liver perfusion and spatial transcriptomics.

Peter Kok-Ting Wan, Ranchu Cheng, David Johnson, Carl Lee, Shihong Wu, Areeb Mian, Ahmet Hazini, Sorayya Moradi, Kate Friesen, Flurin Caviezel and 15 more

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Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

25 authors.

Peter Kok-Ting WanDepartment of Oncology, University of Oxford, Oxford, UK. peter.wan@oncology.ox.ac.uk.
Ranchu ChengDepartment of Oncology, University of Oxford, Oxford, UK.
David JohnsonDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Carl LeeKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Shihong WuDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
Areeb MianNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Ahmet HaziniDepartment of Oncology, University of Oxford, Oxford, UK.
Sorayya MoradiNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Kate FriesenDepartment of Oncology, University of Oxford, Oxford, UK.
Flurin CaviezelDepartment of Oncology, University of Oxford, Oxford, UK.
Syed Hussain AbbasNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Brannon NichollsDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Hatem SadikNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Adil LakhaNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Keaton JonesNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Girishkumar KumaranNuffield Department of Medicine, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.
Matthew J BottomleyNuffield Department of Medicine, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.
Rob JonesDepartment of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Mark ColesKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Rachael Bashford-RogersDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
Constantin CoussiosDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Len SeymourDepartment of Oncology, University of Oxford, Oxford, UK.
Robert CarlisleDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Kerry FisherDepartment of Oncology, University of Oxford, Oxford, UK.
Alex Gordon-WeeksDepartment of Oncology, University of Oxford, Oxford, UK. alex.gordon-weeks@nds.ox.ac.uk.

Funding

Cancer Research UK DRCPGM-Jun25/100008
6 · The paper itself

Abstract

backgroundColorectal liver metastasis (CRLM) is the terminal stage of colorectal cancer and remains largely resistant to immunotherapeutics, yet the underlying immune escape mechanisms remain poorly understood. Through novel observational methods focused on human living and fixed tissue, we profiled the spatial and molecular features of microsatellite stable (MSS) CRLM and the surrounding liver microenvironment.

methodsFirst, we re-purposed normothermic hepatic machine perfusion as a preclinical model of MSS CRLM, enabling delivery of labelled T-cells through physiological vascular routes into living, tumour-bearing human livers. Second, to dissect the liver microenvironment, we spatially map the transcriptomes of MSS CRLM and adjacent liver at single-cell resolution across ~ 1.9 million cells, and perform multiplexed immunofluorescence applying a19-marker panel to a validation cohort.

resultsWhilst T-cells readily extravasated within the peri-tumoural liver, they failed to extravasate into MSS CRLM. Spatial analyses revealed a progressive shift in endothelial phenotypes across regions: from a non-inflamed state in normal liver, to a highly inflamed, peri-tumoural endothelium, and finally to an anergic, angiogenic endothelial population within CRLM characterised by reduced expression of adhesion molecules required for T-cell extravasation. CD4 T-cells that extravasate in the peri-tumoural liver are TCR-reactive yet exhausted, whereas CD4 T-cells within CRLM show stress responses, impaired cytokine gene expression and reduced TCR reactivity, residing within hypoxic niches. These divergent CD4 phenotypes are associated with distinct fibroblast-myeloid niches across peri-tumoural and tumour regions.

conclusionBased on these observations, MSS CRLM impair T-cell extravasation and simultaneously drive intra-tumoural endothelial anergy, peri-tumoural T-cell exhaustion and an intra-tumoural T-cell stress response. Further mechanistic work is needed to validate these findings and guide the development of novel immunotherapeutics.

Indexed as

Clonal AnergyColorectal NeoplasmsEndothelial CellsLiver NeoplasmsT-LymphocytesHumansLiverPerfusionSpatial TranscriptomicsTranscriptomeTumor MicroenvironmentColorectal cancer liver metastasisEendothelial anergyHuman cancer modelsLiver perfusionMultiplexed imagingSpatial transcriptomicsT cell exhaustion

Identifiers

PMID42477793

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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.