However, the TME also poses challenges through soluble NKG2D ligands (e.g., MICA/B) and exosomal factors that downregulate receptor expression or induce exhaustion (13), although NKG2Dζ NK are reported to be resistant to the immunosuppressive TGF-β and soluble NKG2DL in TME of neuroblastoma (76). The gene discussed is KLRK1; the disease is neuroblastoma.