Subsequently, we investigated RNF220’s relationship with the tumor immune microenvironment, where RNF220-high patients exhibited features of immune exhaustion and evasion characterized by decreased overall immune score, reduced CD8+ T-cell infiltration, impaired NK cell activity with increased dormant NK populations, and M0-to-M2 macrophage polarization with suppressed phagocytic capacity. Here, RNF220 is linked to neoplasm.