Inhibitory perturbations: the TME disrupts these pathways through multiple mechanisms: (1) tumour-derived TGF-β and IL-10 downregulate activating receptors (NKG2D, NKp30) and reduce cytokine secretion (IFN-γ↓, CCL3↓/CCL5↓); (2) immune checkpoint ligands (PD-L1) and stromal cells (Treg, TAM) reinforce suppression—Tregs secrete TGF-β to block granzyme B expression, whereas TAMs increase adenosine signalling to inhibit NK cell activation [52, 53]; and (3) hypoxia (marked by HIF-1α↑) induces VEGF secretion, shifting NK cells towards a pro-angiogenic state rather than a cytotoxic state. The gene discussed is TGFB1; the disease is neoplasm.