Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer

Abstract

PD-L1 (programmed cell death 1 ligand 1) expression is a major immune suppressive mechanism via engagement of the PD-1 (programmed cell death protein 1) and PD-L1 axis in non–small-cell lung cancer (NSCLC). After antigen recognition and activation of T cells through a T-cell receptor and major histocompatibility complex peptide-based interaction, PD-L1 can act as a coregulatory signal through binding of the inhibitory PD-1 receptor that ultimately leads to inactivation of lymphocytes and other immune cells.^1-3 Under certain circumstances, such as viral infections, this mechanism can act as a checkpoint to limit the immune response and avoid tissue damage.^4,5 This mechanism can also mediate immune tolerance as seen by placental trophoblastic expression, thereby preventing autoimmune-based destruction of this new immunologically foreign organ.^6-9 Similarly, tumor cells can evade the immune response through up-regulation of PD-L1, with diverse human malignant tumors showing elevated levels of PD-L1 protein, including NSCLC.^10-14