Tumor immune evasion arises through loss of TNF sensitivity

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Science Immunology  18 May 2018:
Vol. 3, Issue 23, eaar3451
DOI: 10.1126/sciimmunol.aar3451

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Killing without poking holes

Given the success of T cell–centric cancer immunotherapies, there is considerable interest in understanding exactly how tumors evade this form of therapy. Kearney et al. carried out a series of genome-wide CRISPR screens to identify mechanisms of tumor immune evasion from cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. They found IFN-γ signaling and antigen presentation to be critical for CTL-mediated killing of cancer cells and uncovered TNF signaling as a key effector mechanism for both CTL and NK cell antitumor activity. The same immune evasion mechanisms arose upon screening with perforin-deficient CTLs, suggesting that tumors evade the immune system by dampening the effects of cytokines, not direct killing via perforin.