We investigated the interplay between PD-L1, COX-2, 15-hydroxy prostaglandin dehydrogenase (15-PGDH), and TILs using both an internal immunohistochemistry (IHC)-based CRC cohort (n = 320) and large public transcriptomic datasets (GSE39582, TCGA-COAD, and E-MTAB-12862). This evidence concerns the gene CD274 and colorectal carcinoma.