Spatial proteomics further indicates that PTMs are patterned rather than randomly dispersed within the tumor microenvironment: hypoxic niches exhibit elevated PAD4 and O-GlcNAc transferase (OGT) activity, forming localized PTM “hotspots” that coincide with immune-exclusion zones in PDAC (Figure 2) [43,44,45]. Here, PADI4 is linked to neoplasm.