Abstract
Cancer Immunology Given the success of T cell–centric cancer immunotherapies, there is considerable interest in understanding exactly how tumors sometimes evade this form of treatment. 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. Interferon-γ signaling and antigen presentation were critical for CTL-mediated killing of cancer cells, and TNF (tumor necrosis factor) signaling was 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, rather than reducing direct killing via perforin. Sci. Immunol. 3 , eaar3451 (2018).
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