The role of immune checkpoint inhibitors and/or Yttrium-90 radioembolization in the management of hepatocellular carcinoma: challenges of treatment sequence

Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer secondary to chronic liver disease or cirrhosis. In the setting of chronic inflammation, the liver’s tightly regulated immune system is disrupted, resulting in immune cell fatigue. This makes the liver vulnerable to tumorigenesis. Surgery and/or transplantation offer the best long-term survival for patients diagnosed with early HCC. Unfortunately, patients commonly develop recurrent or metastatic disease. Some patients will present with unresectable HCC or liver dysfunction. As such, locoregional therapy options may be limited. Research is focused on leveraging the distinctive liver immune microenvironment and its role in HCC carcinogenesis for the development of more effective systemic therapies. Given the success of immunotherapy in treating advanced HCC, the scientific community is looking to expand the indications of immunotherapy to the neoadjuvant and/or adjuvant setting and in combination with other locoregional therapies. We herein review the most recent data on the use of neoadjuvant or adjuvant immunotherapy and its combination with Yttrium-90 (Y90) radioembolization for HCC for curative intent.