Tumor hepatocyte-derived VEGFA induces DLL4+ PLVAP+ tumor ECs, the ECs initiate reprogramming of the macrophages by triggering Notch signaling, and the FOLR2+ macrophages expressing a multitude of immunoregulatory chemokines and cytokines recruit Tregs, forming the immunosuppressive environment in HCC. Here, PLVAP is linked to hepatocellular carcinoma.