Targeting the PD-1/PD-L1 interaction in nasopharyngeal carcinoma

Upregulation of the programmed cell death receptor-1 and ligand (PD-1/PD-L1) pathway is one of many possible mechanisms of immune-evasion relevant to Epstein-Barr virus (EBV)- associated nasopharyngeal cancer (NPC). The therapeutic targeting of the PD-1/ PD-L1 axis is an area of active research in NPC and at least 8 monoclonal or bi-specific antibodies targeting this axis are currently under clinical evaluation in some of the following clinical settings: (1) palliative treatment of recurrent and/or metastatic (R/M) disease; (2) radical treatment of locoregionally advanced disease in adjunct to conventional chemoradiotherapy; (3) local/ regional recurrence. PD-1 antibodies as monotherapy has been reported to yield an overall objective response in around 20-30% of patients with R/M NPC in single-armed phase II trials, and the predictive role of PD-L1 expression in NPC remains to be defined. As with other solid tumors, combinatorial strategies with cytotoxic chemotherapy, radiotherapy or other immunotherapeutic agents (such as other immune-checkpoint inhibitors, EBV-targeting cellular therapy and other immune-modulating agents) and vascular endothelial growth factor/receptor antibodies are actively being evaluated in clinical trials with single-armed or randomized designs. This article will review the scientific rationale of targeting the PD1/PD-L1 axis in NPC, and summarizes the latest trials involving these agents and predictive biomarkers of response to PD-1/PD-L1 antibodies in NPC.