First, an intrinsic (innate) resistance is caused by constitutive PD-L1 expression in tumor cells that can be induced by oncogenic signaling pathways activated in different tumors, such as PI3K/AKT [13,14], signal transducer and activator of transcription (STAT)-3 [15], epidermal growth factor receptor (EGFR) [16], cyclin-dependent kinase 5 (Cdk5) [17], and MYC pathways [18], or by genetic changes. The gene discussed is CD274; the disease is neoplasm.