Immune Checkpoint Blockade is a powerful new weapon against cancer. Unfortunately, only a fraction of patients achieve remission. Current research is directed towards finding biomarkers that would help identify likely responders and develop new therapeutic approaches to transform non-responders to responders. This symposium will provide a historical perspective on the field of immune-oncology and discuss recent progress in identifying new strategies for boosting the efficacy of immune checkpoint inhibitors through combination therapy with ATM and DNA methylation transferase inhibitors.