Fig. 1 |. Mapping core genes and pathways for cancer-intrinsic CTL evasion.
a, Mouse cell lines screened in this study. Renca, renal carcinoma; B16, melanoma; 4T1 and EMT6, breast carcinoma; CT26 and MC38, colorectal carcinoma. HA and Ova refer to haemagglutinin and ovalbumin antigens, respectively. Cell lines with the C57BL/6 genotype are in grey, and those with the BALB/c genotype are in black. b, Workflow for mTKO genome-scale pooled CRISPR screens to identify fitness and CTL-evaslon genes. E:T, effector-to-target cell ratio; KO, knockout. The essential gene and non-essential gene distributions are based on gene-level fold-change values, where fold change = log2(normalized read counts at early or late time points) − log2(normalized T0 read counts). c, Rank-ordered normalized z-score (NormZ score) at the mid time point for all six CTL killing screens. Hits at FDR < 5% are highlighted in yellow (resistor genes) and blue (sensitizer genes). The top ten resistor and sensitizer genes are indicated. Dot size is inversely scaled by FDR. d, Genetic co-similarity map for cancer-intrinsic CTL evasion. Representative pathways enriched in a cluster are shown on the diagonal axis (FDR < 1%). ETC, electron transport chain; PCC, Pearson correlation coefficient. e, Daisy model of gene essentiality, adapted for core cancer-intrinsic CTL-evasion genes. Each cancer cell line is represented as a petal on the flower. f, Distribution of cancer-intrinsic CTL-evasion genes at FDR < 5% across the six cell lines. g, Pathway themes enriched in core cancer-intrinsic CTL-evasion genes (FDR < 5%). −log10(P) represents the −log10 of the adjusted P value (FDR). Mean percentage overlap refers to the mean of the percentage of overlapping core cancer-intrinsic CTL-evasion and pathway-definition genes across all pathways in a theme. For each theme, the mean number of query genes contained in the pathway/mean pathway term size is displayed to the right of each bar.