Spontaneous and therapeutic immune responses in hepatocellular carcinoma: implications for current and future immunotherapies.

Hepatocellular carcinoma (HCC) represents a major health problem in the world, ranking fifth in incidence and third in cancer-related deaths. Due to the unique immunosuppressive microenvironment of the liver, HCC develops in an immunotolerant niche posing an important obstacle to immunotherapy. A number of studies, however, have shown immunogenic properties of HCC by demonstrating spontaneous adaptive immune responses during tumor formation and progression. Furthermore, studies examining immune responses during HCC therapy have revealed that conventional treatments such as surgical resection, locoregional therapy and systemic therapy with antibodies, small molecules or chemotherapy induce adaptive immune responses that contribute to therapeutic effects. These observations have provided a basis for clinical trials involving adoptive transfers of T cells or natural killer cells, peptide and dendritic cell vaccinations or, more recently, virotherapy and inhibition of co-inhibitory molecules. Here, spontaneous and therapeutic immune responses in HCC and their implication for current and future immunotherapies are discussed.