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.

Automated summary

The upregulation of the PD-1/PD-L1 pathway is a possible immune-evasion mechanism in Epstein-Barr virus-associated nasopharyngeal cancer (NPC). Therapeutic targeting of this pathway is actively researched in NPC, with multiple monoclonal antibodies currently under evaluation in clinical settings. Combinatorial strategies involving cytotoxic chemotherapy, radiotherapy, and other immunotherapeutic agents are also being explored in clinical trials for NPC.