Journal article
Tumor immune evasion arises through loss of TNF sensitivity
CJ Kearney, SJ Vervoort, SJ Hogg, KM Ramsbottom, AJ Freeman, N Lalaoui, L Pijpers, J Michie, KK Brown, DA Knight, V Sutton, PA Beavis, I Voskoboinik, PK Darcy, J Silke, JA Trapani, RW Johnstone, J Oliaro
Science Immunology | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2018
Abstract
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)–based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon- (IFN-) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell–mediated killing and blunted antitumor immune responses in vivo. Deletion of a number of genes in the TNF pathway also emerged as..
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Funding Acknowledgements
S.J.V. was funded by a Rubicon fellowship from the Netherlands Organization for Scientific Research; R.W.J. by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow Fellowship, project and program grants, Cancer Council Victoria, and the Victorian Cancer Agency grants; C.J.K. by an NHMRC Early Career Fellowship; S.J.H. by a Peter MacCallum Foundation grant; and J.O. and I.V. by NHMRC project grants. General funding and support provided by the Australian Cancer Research Foundation.