Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity

ABSTRACT: 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. 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-y production decoupled from TCR signalling, decreased polyfunctionality and reduced central memory (TCM) formation. Modelling of T-cell-tumour interactions with a tumour organoid platform revea

SUBMITTER: Dr. Alastair Copland 

PROVIDER: S-SCDT-10_1038-S44321-024-00159-2 | biostudies-other |

REPOSITORIES: biostudies-other