This seemingly paradoxical relationship between PD-L1 expression, poor prognosis, and ICI responsiveness may reflect both the spatial heterogeneity of PD-L1 expression in tumor cells and its dynamic regulation: inducible PD-L1 upregulation by IFN−γ released during an active anti-tumor immune response versus constitutive PD-L1 expression driven by HIF−1α in hypoxic regions (127). Here, IFNG is linked to neoplasm.