Journal article

Intracellular zinc protects tumours from T cell-mediated cytotoxicity

EJ Lelliott, J Naddaf, K Ganio, J Michie, S Wang, L Liu, N Silke, A Ahn, KM Ramsbottom, AJ Brennan, AJ Freeman, S Goel, SJ Vervoort, CJ Kearney, PA Beavis, CA McDevitt, J Silke, J Oliaro

Cell Death and Differentiation | SPRINGERNATURE | Published : 2024

Abstract

Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour c..

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