While constitutive oncogenic signals (such as protein kinase B (AKT), epidermal growth factor receptor (EGFR), KRAS pathways) upregulate PD-L1 expression on tumors as innate (tumor cell intrinsic) resistance (Fig. 1, left) [44–48], inflammatory signals generate cytokine-induced PD-L1 expression on either tumor cells or immune cells (myeloid suppressor cells, dendritic cell, macrophage, and lymphocytes) in the tumor microenvironment as adaptive resistance (Fig. 1, right) [49, 50]. The gene discussed is CD274; the disease is neoplasm.