Therapeutic Targeting of Checkpoint Receptors within the DNAM-1 Axis.

Therapeutic antibodies targeting the CTLA-4/ PD-1 pathways have revolutionized cancer immunotherapy by eliciting durable remission in cancer patients. However, relapse following early response, attributable to primary and adaptive resistance, is frequently observed. Additional immunomodulatory pathways are being studied in patients with primary or acquired resistance to CTLA-4 or PD-1 blockade. The DNAM-1 axis is a potent co-regulator of innate and adaptive immunity whose other components include the immunoglobulin receptors TIGIT, PVRIG and CD96, and their nectin and nectin-like ligands. We review the basic biology and therapeutic relevance of this family, which has begun to show promise in cancer clinical trials.