The Immunobiology of Hepatocellular Carcinoma in Humans and Mice: Basic Concepts and Therapeutic Implications.

Basic and clinical studies have demonstrated the efficacy of immunotherapy, a technical and conceptual breakthrough that has revolutionized cancer treatment. Hepatocellular carcinoma (HCC), a deadly malignancy with etiologic diversity and a chronic course, is strongly influenced by the immune system, and was recently found to partially benefit from immune checkpoint inhibitor therapy. Notably, HCC onco-immunology depends on diverse genetic and environmental factors that together shape cancer-promoting inflammation as well as immune dysfunction, critical processes that control HCC malignant progression and response to therapy. Here we summarize current understanding of liver and HCC oncoimmunology obtained through basic studies with mouse models and clinical practice in humans. In particular, we discuss preclinical and clinical findings that implicate immunomodulation as a major factor in HCC development and explain the basis for HCC-targeting immunotherapy. LAY SUMMARY: Chronic inflammation and immune dysfunction are important contributors to the onset and progression of the most common form of liver cancer-hepatocellular carcinoma (HCC). Although progress in HCC treatment and prevention has been slow, recent studies suggest that immune-based cancer therapies may revolutionize its treatment. We explain the basic concepts and clinical science underlying a portion of the patient population. However, many challenges for future research remain, including improved methodology for identifying patients likely to benefit from HCC immunotherapy and discovery of supplements that can further augment therapeutic response rates to HCC immunotherapy.