Fig. 1: Identification of NEDD8 as a TNBC vulnerability against nivolumab in genome-wide CRISPR screens.

a Primary human lymphocytes (300,000 per well) were co-cultured with MDA-MB-231 cells in a 96-well flat bottom plate ±10 μg/ml nivolumab (red) or durvalumab (blue). Levels of soluble granzyme B or interferon γ (IFNγ) in culture supernatants were measured on day 5 by ELISA, mean ± SD, unpaired two-tailed T-test. Each symbol represents an individual lymphocyte donor (n = 4). b Schematic illustration and (c) the 9 overlapping hits from the genome-wide CRISPR screens when comparing co-cultures ±10 μg/ml nivolumab. d Demonstration of the 9 commonly depleted genes according to individual gRNAs performance (depleted gRNAs in blue and enriched gRNAs in red). e Analysis of the clinical relevance of NEDD8 mRNA expression in breast cancer patients receiving paclitaxel in combination with pembrolizumab (n = 69) as part of the I-SPY2 neoadjuvant platform trial. Source data are provided as a source data file.