**Competing interests**

No competing interests exist among the authors.

### **Keypoints**

Based on the outcomes of recent clinical trials, it appears that a single agent may not be sufficient for treating HCC; consequently, combination therapy characterizes an important area of research for the systemic treatment of advanced HCC. Moreover, ICIs are now being considered as part of HCC treatments, and their use in combination with molecular targeted therapy is shown to be an effective way to boost the immune system's response. The combined therapy of atezolizumab/bevacizumab is the first-line treatment to receive regulatory approval.

Immune checkpoint inhibitors (ICIs) may potentially be effective at earlier stages of illness. Combination therapies are being investigated in the intermediate stage in combination with or in place of transarterial chemotherapy, which is currently the standard of care. ICIs are also being explored as adjuvant and neoadjuvant therapy in the setting of early and very early surgery or ablation.

New research reveals that the control of the commensal gut microbiome and hepatic antitumor immunity are linked. Moreover, ICIs have been linked to immunerelated side effects. In HCC clinical studies, however, the prevalence of grade 3/4 incidents was moderate. Therefore, ICIs are largely considered to be a choice in advanced HCC patients.

*Emerging Immunotherapy: Liver Cancer Microenvironment for Treatment DOI: http://dx.doi.org/10.5772/intechopen.106021*
