Figure 3: Targeted in vivo screening identifies subunits of the INO80 and BAF complexes that limit T cell persistence.

(A) Diagram of in vivo pooled CRISPR screening. (B) Correlation of tumor LFC z-scores to spleen LFC z-scores, colored by functional category. (C) Correlation of in vivo z-score and in vitro z-scores for genes in the CRISPR mini-pool. (D) Correlation of in vivo MC-38 and B16 tumor z-scores for genes in the CRISPR mini-pool. (B-D) Results shown are merged from 3 mice per tumor model (n=6 tumors, n=3 spleens). (E) Cytoscape protein-protein interaction network colored by z-score in MC-38 tumors. (F) Top: Boxplot of MC-38 tumor versus input log fold change for each sgRNA targeting the indicated gene, with the mean control log fold change subtracted. Bottom: heatmaps showing the sgRNA average of the indicated in vivo or in vitro screen for the same hits. Box plots show 25^th, 50^th (median), and 75^th percentiles with outliers shown as dots. Each dot represents one sgRNA-replicate, n=36 per target gene. (G) Individual sgRNA-replicate z-scores for six top hits showing the MC-38 Tumor vs Input comparison (left, n=36), MC-38 Spleen vs Input (center, n=18), and in vitro Chronic vs Acute (right, n=12). See also Figure S6 and Tables S2–3.