The tumor microenvironment, which critically influences ICI responsiveness, drives immune evasion and therapy resistance via multiple mechanisms: impaired immune checkpoint signaling (PD-1/PD-L1, CTLA-4/B7), defective T-cell infiltration, immunosuppressive cell expansion (MDSCs, TAMs), and immunoediting-induced T-cell exhaustion [48–53]. Here, CTLA4 is linked to neoplasm.