Extended Data Figure 8. A requirement for the mevalonate/cholesterol synthesis enzymes for TIL persistence and heightened antitumor activity in a melanoma model.

a, GSEA of the mevalonate/cholesterol synthesis pathway in genes pre-ranked by their impact on TIL accumulation in B16-OVA tumors from a published CRISPR/Cas9-mediated loss-of-function screen. b, Dimensionality reduction plot by UMAP of WT and Regnase-1 KO OT-I cells profiled from MC38-GP_33–41 tumors by scRNAseq 7 days after adoptive transfer (left) and unsupervised hierarchical clustering heatmap of selected genes related to CD8 T cell cytotoxicity (Ifng) stemness (Tcf7), proliferation (Mki67), and the mevalonate/cholesterol synthesis pathway (Srebf2, Hmgcs1, Fdft1, Hmgcr, and Ldlr) grouped by cell type and cluster. c, Comparison of the effect of targeting the 50 genes of the mevalonate/cholesterol pathway included in our targeted screen in WT TIL or Regnase-1 KO TIL (sgZc3h12a) from a published CRISPR/Cas9-mediated loss-of-function screen in B16 melanoma tumors³². Relevant enzymes are labeled.