Our single-cell data analysis extends this by revealing iCAFs as central orchestrators of such dysfunction: they secrete IL-6/LIF to polarize macrophages toward M2 states while recruiting Tregs via CXCL12—mirroring PPY-induced iCAF mechanisms in pancreatic cancer that suppress CD8+ T cells through EGFR/NF-κB [20,50]. This evidence concerns the gene CD8A and pancreatic neoplasm.