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Evanthia T. Roussos Torres, MD, PhD, Keck School of Medicine of USC, Los Angeles, CA, discusses the rationale behind combining epigenetic modulating agents with immune checkpoint blockade in cancer, highlighting preclinical investigations, as well as the combination of entinostat, nivolumab and ipilimumab currently evaluated in patients with advanced HER2-negative breast cancer. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.