Journal article

Unleashing TNF cytotoxicity to enhance cancer immunotherapy

Andrew J Freeman, Conor J Kearney, John Silke, Jane Oliaro



Tumor necrosis factor (TNF) is a proinflammatory cytokine that is produced and secreted by cytotoxic lymphocytes upon tumor target recognition. Depending on the context, TNF can mediate either pro-survival or pro-death signals. The potential cytotoxicity of T cell-produced TNF, particularly in the context of T cell-directed immunotherapies, has been largely overlooked. However, a spate of recent studies investigating tumor immune evasion through the application of CRISPR-based gene-editing screens have highlighted TNF-mediated killing as an important component of the mammalian T cell antitumor repertoire. In the context of the current understanding of the role of TNF in antitumor immunity, w..

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Awarded by NHMRC

Awarded by National Breast Cancer Foundation

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

A.J.F. was supported by scholarships from Australian Commonwealth Government, Steer North Australia, and the Peter MacCallum Cancer Foundation. C.J.K. was supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship. J.S. was supported by a NHMRC Research Fellowship (1195038) . J.O. was supported by NHMRC (1139626) and National Breast Cancer Foundation (IIRS-18-151) project grants.