Hepatocellular carcinoma (HCC) is the most common liver cancer and a relevant global health problem. Immune checkpoint inhibitors (ICIs) represent the most effective systemic treatment for HCC. However, due to primary resistance, approximately 40% of HCC patients do not achieve a disease control with ICIs. Moreover, a similar proportion will experience disease progression after an initial response caused by secondary resistance. This review describes the mechanisms of primary and secondary resistance and reports the ongoing therapeutic strategies to overcome these obstacles.
Keywords: atezolizumab; bevacizumab; cirrhosis; durvalumab; hepatocellular carcinoma; immune checkpoint inhibitors; immunotherapy; liver cancer; outcome; resistance; tremelimumab; tumour microenvironment.