Y90 Radioembolization Combined with Immune Checkpoint Blockade in an Animal Model of Hepatocellular

Radioembolization for hepatocellular carcinoma (HCC) has demonstrated improved time to progression, quality of life, and survival compared to transarterial chemoembolization. However, therapeutic efficacy in intermediate stage disease is limited, with median survival of approximately 18 months. There is a critical need for optimizing this treatment to prevent recurrence, prolong survival, and potentially provide curative intent. Immunotherapy, a novel treatment option for cancer, may serve to meet this need. Specifically, immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), have demonstrated response in HCC, with response rates with the newest agent Nivolumab of 20% in advanced disease. While this agent has been approved for use in HCC, optimization of this treatment requires study. The objective of this proposal is to characterize the immune response to radioembolization to determine the optimal time period in which to initiate immunotherapy. Characterization of this response will determine the appropriate timing of these two therapies in combination to maximize efficacy. We propose studying these effects in a rat model of HCC.