Using gene set enrichment analysis (GSEA) with all genes ranked according to the fold change (FC) between C2 and C4 subtypes, we found that terminally exhausted CD8+ T cell and TGF-beta signaling signatures were upregulated in the C2 subtype in the CRC-AFFY (Figure 1H) and CRC-RNAseq (Figure 1—figure supplement 3G) cohorts, which might reveal that CD8+ T cell infiltration within the tumor bed was suppressed by the stroma and was in a late state of exhaustion. This evidence concerns the gene CD8A and neoplasm.