Figure 2.

PD-L1 expression in the tumor microenvironment may demonstrate adaptive or constitutive expression patterns. Left panels: In adaptive PD-L1 expression, tumor and/or immune cell PD-L1 expression is geographically associated with tumor-infiltrating lymphocytes. This finding is consistent with cytokine (primarily IFN-γ) mediated adaptive immune resistance. Upper left panel: Schematic of PD-L1-mediated adaptive immune resistance. Tumor cells are shown in green, macrophages are purple, and TIL are orange. PD-L1 expression on the surface of the cells is denoted by a thick black line. Lower left panel: Photomicrograph shows a subcutaneous deposit of metastatic melanoma stained with immunohistochemistry for PD-L1 expression. PD-L1 expression is evident on tumor cells as well as immune cells at the host–tumor interface (×200, original magnification). Upper right panel: Schematic showing constitutive (non-immune cell associated/diffuse) PD-L1 expression on the surface of tumor cells. Such a pattern of PD-L1 expression is likely driven by tumor intrinsic factors, such as oncogenic pathways or PD-L1 gene amplification. Lower right panel: Photomicrograph of primary head and neck squamous cell carcinoma stained with immunohistochemistry for PD-L1 expression (×250, original magnification). PD-L1 expression is displayed on nearly every tumor cell and is independent of an immune infiltrate. Combined patterns of adaptive and constitutive expression may also be observed (not shown).