Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is among the most common cancer diseases worldwide and has only limited treatment options at advanced disease stages. Activation of the immune system with checkpoint inhibitors has revolutionized cancer medicine and has become important also for HCC treatment. Here, we summarize the current status of immunotherapy options for HCC and highlight how combination with locoregional therapies could improve the outcome of patients. Novel pathways and targets for immunologic drug development are briefly discussed that could help to increase the response rate of these approaches in HCC. ABSTRACT: Background: Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic “door” to improve outcome and response rate for patients with HCC. Methods: Published data on HCC experimental to pre-(clinical) treatment strategies from standard of care to novel immunomodulatory concepts were summarized and discussed in detail. Results: Overall, our knowledge of the role of immune checkpoints in HCC is dramatically increased in the last years. Experimental and pre-clinical findings could be translated to phase 1 and 2 clinical trials and became standard of care. Local ablative techniques of HCC could improve the effectivity of immune checkpoint inhibitors in situ. Conclusions: This review demonstrates the importance of immunomodulatory treatment strategies of HCC, whereby the “best treatment code” of immune checkpoint drugs, combination with ablative techniques and of timing must be evaluated in coming clinical trials.