BibTex format
@article{Copland:2024:10.1038/s44321-024-00159-2,
author = {Copland, A and Mackie, GM and Scarfe, L and Jinks, E and Lecky, DAJ and Gudgeon, N and McQuade, R and Ono, M and Barthel, M and Hardt, W-D and Ohno, H and Hoevenaar, WHM and Dimeloe, S and Bending, D and Maslowski, KM},
doi = {10.1038/s44321-024-00159-2},
journal = {EMBO Mol Med},
pages = {3057--3088},
title = {Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity.},
url = {http://dx.doi.org/10.1038/s44321-024-00159-2},
volume = {16},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica 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) and IFNγ reporter mice (Nr4a3-Tocky-Ifnγ-YFP) and a colorectal cancer (CRC) model to interrogate T cell activity during BCT with attenuated STm. We found that colonic tumour infiltrating lymphocytes (TILs) exhibited a variety of activation defects, including IFN-γ production decoupled from TCR signalling, decreased polyfunctionality and reduced central memory (TCM) 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 ansB 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.
AU - Copland,A
AU - Mackie,GM
AU - Scarfe,L
AU - Jinks,E
AU - Lecky,DAJ
AU - Gudgeon,N
AU - McQuade,R
AU - Ono,M
AU - Barthel,M
AU - Hardt,W-D
AU - Ohno,H
AU - Hoevenaar,WHM
AU - Dimeloe,S
AU - Bending,D
AU - Maslowski,KM
DO - 10.1038/s44321-024-00159-2
EP - 3088
PY - 2024///
SP - 3057
TI - Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity.
T2 - EMBO Mol Med
UR - http://dx.doi.org/10.1038/s44321-024-00159-2
UR - https://www.ncbi.nlm.nih.gov/pubmed/39558103
VL - 16
ER -