Immunotherapy is revolutionizing the clinical management of a variety of cancers, including hepatocellular carcinoma (HCC), a type of liver cancer that shows little response to conventional therapeutic approaches. Recently, two immune checkpoint inhibitors, nivolumab (Opdivo) and pembrolizumab (Keytruda), have been approved as second line therapy after showing unprecedented complete responses in clinical trials. However, not all patients are sensitive to these anti-PD1 drugs, highlighting the urgent need to identify biomarkers for optimal patient selection and strategies to overcome resistance. Dr. Lujambio is using a novel mouse model of liver cancer and samples from HCC patients treated with checkpoint inhibitors to identify genes that are involved in intrinsic and acquired resistance to this therapy. These findings will be critical to define biomarkers that identify HCC patients who are most likely to benefit from this immunotherapy. Moreover, her findings may lead to the design of combination therapies that effectively treat more patients.