The PD-1 immune checkpoint pathway, which comprises the PD-1 T-cell coinhibitory receptor and its ligands PD-L1 and PD-L2 expressed on tumor and immune cells in the tumor microenvironment, mediates local immune resistance. Monoclonal antibodies blocking this pathway are active against advanced tumors of several different types, providing a "common denominator" for cancer therapy. PD-L1 expression in pretreatment tumor specimens may identify patients and tumor types that are more likely to have a response to PD-1 pathway blockade. An elevated tumor mutational burden or association with viral carcinogenesis, creating new determinants for immune recognition, has also been associated with tumor regressions in individual patients and the responsiveness of tumor subtypes to anti-PD-1 therapy.