Several intrinsic oncogenic mechanisms responsible for the immunosuppression in pancreatic cancer have been identified, including the Kras mutation [67,68], the CDKN2A mutation [69], the TGF-beta within the TME [70], the activation of WNT/beta-catenin signaling [71], PTEN loss, and PI3K–AKT pathway activation [72,73,74,75,76], which were all highly enriched in TMEscore-low tumors. Here, CDKN2A is linked to familial pancreatic carcinoma.