Decoding spatial mTOR signalling reveals distinct roles in the tumour microenvironment.
6 affiliations
- 1School of Cancer and Pharmaceutical Sciences, Stamford St., Franklin Wilkins Building, King's College London, London, UK.
- 2Tissue Image Analytics Center, University of Warwick, Coventry, UK.
- 3Nuffield Department of Surgical Sciences, Level 6, John Radcliffe Hospital, University of Oxford, Oxford, UK.
- 4GE HealthCare Technology and Innovation Center, Niskayuna, NY, USA.
- 5School of Cancer and Pharmaceutical Sciences, Stamford St., Franklin Wilkins Building, King's College London, London, UK. [email protected].
- 6Department of Engineering Science, Old Road Campus Research Building, University of Oxford, Oxford, UK. [email protected].
Abstract
The tumour microenvironment comprises a variety of cell types that interact with malignant cells, influencing both cancer progression and the patient response to therapy. Given the intricate interactions among these components, assessing how signalling pathways contribute to cancer progression by acting on different components of the TME is particularly complex. Multiplexed imaging allows simultaneous assessment of signalling in multiple of these components. Here, we utilise a highly multiplexed dataset of 61 markers across 746 colorectal tumours to investigate how complex mTOR signalling in different tissue compartments influences patient prognosis. We found that mTOR pathway signalling in immune cells correlates with favourable patient survival. Advanced spatially-aware analysis of signalling activities using graph neural networks revealed that the positive association between immune mTOR signalling and patient survival was more pronounced in tumours with features of a more differentiated morphology. Integrative analysis using TCGA data and spatial transcriptomics confirmed a role for immune mTOR signalling in immune activation, accompanied by reduced TGF-β signalling. Our work highlights the importance of adopting a personalised approach to targeting mTOR in cancer patients and establishes a framework for studying cell type-specific signalling in the TME.
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BibTeX
@article{zuhair2026decoding,
title = {{Decoding spatial mTOR signalling reveals distinct roles in the tumour microenvironment.}},
author = {Razan Zuhair and Mark Eastwood and Megan Bradbury and Amy Cross and Joanna Hester and Fadi Issa and Fiona Ginty and Heba Z Sailem},
journal = {NPJ precision oncology},
year = {2026},
month = sep,
doi = {10.1038/s41698-026-01674-w},
url = {https://europepmc.org/article/MED/42875457},
note = {CC BY},
}
RIS
TY - JOUR
TI - Decoding spatial mTOR signalling reveals distinct roles in the tumour microenvironment.
AU - Razan Zuhair
AU - Mark Eastwood
AU - Megan Bradbury
AU - Amy Cross
AU - Joanna Hester
AU - Fadi Issa
AU - Fiona Ginty
AU - Heba Z Sailem
PY - 2026
DA - 2026/09/25
JO - NPJ precision oncology
DO - 10.1038/s41698-026-01674-w
UR - https://europepmc.org/article/MED/42875457
AB - The tumour microenvironment comprises a variety of cell types that interact with malignant cells, influencing both cancer progression and the patient response to therapy. Given the intricate interactions among these components, assessing how signalling pathways contribute to cancer progression by acting on different components of the TME is particularly complex. Multiplexed imaging allows simultaneous assessment of signalling in multiple of these components. Here, we utilise a highly multiplexed dataset of 61 markers across 746 colorectal tumours to investigate how complex mTOR signalling in different tissue compartments influences patient prognosis. We found that mTOR pathway signalling in immune cells correlates with favourable patient survival. Advanced spatially-aware analysis of signalling activities using graph neural networks revealed that the positive association between immune mTOR signalling and patient survival was more pronounced in tumours with features of a more differentiated morphology. Integrative analysis using TCGA data and spatial transcriptomics confirmed a role for immune mTOR signalling in immune activation, accompanied by reduced TGF-β signalling. Our work highlights the importance of adopting a personalised approach to targeting mTOR in cancer patients and establishes a framework for studying cell type-specific signalling in the TME.
SN - 2397-768X
ER -