Imperial College London
Portrait Picture

DrMasahiroOno

Faculty of Natural Sciences, Department of Life Sciences

Reader in Immunology
 
 
 
//

Contact

 

m.ono

 
 
//

Location

 

605Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Copland:2023:10.1101/2023.01.12.523780,
author = {Copland, A and Mackie, GM and Scarfe, L and Lecky, DAJ and Gudgeon, N and McQuade, R and Ono, M and Barthel, M and Hardt, W-D and Ohno, H and Dimeloe, S and Bending, D and Maslowski, KM},
doi = {10.1101/2023.01.12.523780},
title = {<i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity},
url = {http://dx.doi.org/10.1101/2023.01.12.523780},
year = {2023}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Summary</jats:title><jats:p>Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours.<jats:italic>Salmonella enterica</jats:italic>Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A longstanding paradox is the redundancy of T cells for treatment efficacy; instead, STm BCT depends on innate phagocytes for tumour control. Here, we used distal T cell receptor (TCR) reporter mice (<jats:italic>Nr4a3-Tocky-Ifng-YFP</jats:italic>) and a colorectal cancer (CRC) model to interrogate T cell activity during BCT with attenuated STm. We found that colonic TILs exhibited a variety of activation defects, including IFN-γ production decoupled from TCR signalling, decreased polyfunctionality and reduced T<jats:sub>CM</jats:sub>formation. Modelling of T-cell–tumour interactions with a tumour organoid platform revealed an intact TCR signalosome, but paralysed metabolic reprogramming due to inhibition of the master metabolic controller, c-Myc. Restoration of c-Myc by deletion of the bacterial asparaginase<jats:italic>ansB</jats:italic>reinvigorated T cell activation, but at the cost of decreased metabolic control of the tumour by STm. This work shows for the first time that T cells are metabolically defective during BCT, but also that this same phenomenon is inexorably tied to intrinsic tumour suppression by the bacterial vector.</jats:p>
AU  - Copland,A
AU  - Mackie,GM
AU  - Scarfe,L
AU  - Lecky,DAJ
AU  - Gudgeon,N
AU  - McQuade,R
AU  - Ono,M
AU  - Barthel,M
AU  - Hardt,W-D
AU  - Ohno,H
AU  - Dimeloe,S
AU  - Bending,D
AU  - Maslowski,KM
DO  - 10.1101/2023.01.12.523780
PY  - 2023///
TI  - <i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity
UR  - http://dx.doi.org/10.1101/2023.01.12.523780
ER  -
Download