PIK3CA and neoplasm: This establishes a potent positive feedback loop (“PD-L1 → PI3K/Akt → EMT → PD-L1”), which locks the tumor into a highly aggressive, metastatic, and simultaneously immune-evasive state, further amplifying the pro-invasive signals from both the fibrotic microenvironment and the tumor's intrinsic PI3K/Akt dysregulation.