NK cell immune evasion occurs through loss of TNF pathway members.

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NK cell immune evasion occurs through loss of TNF pathway members. NK cell immune evasion occurs through loss of TNF pathway members. (A) Experimental design of CRISPR/Cas9 screening for resistance to NK cell killing. (B) NK cell–MC38 killing assay (18 hours) at the indicated E:T ratios. (C) NK cells were cocultured with MC38 cells at the indicated E:T ratios. After 6 hours, cytokines were measured by cytometric bead array. (D) MC38 cells were subjected to three rounds of exposure to primary mouse NK cells, as described in (A), followed by sequencing for the top enriched genes. (E) Protein network analysis from the top hits identified in (D). (F) GO term analysis from the top hits identified in (D). TRAIL, TNF-related apoptosis-inducing ligand. (G) Comparison of the top scoring genes in screens described in (D) and the OT-I T cell screen described in Fig. 1C. (H) Schematic representation of immune evasion from NK attack. DISC, death-inducing signaling complex. Conor J. Kearney et al. Sci. Immunol. 2018;3:eaar3451 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works