Oncogenic mutations or gene expression changes in cancer cells can activate or inhibit various signaling pathways, such as the interferon-γ (IFN-γ), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) pathways, which can affect PD-L1 expression (Figure 3) and the TME, ultimately impacting ICI therapy efficacy. Here, TNF is linked to cancer.