Comparison of immune profiles between hepatocellular carcinoma subtypes

Abstract Immunotherapy, especially immune checkpoint inhibitors, is becoming a promising treatment for hepatocellular carcinoma (HCC). However, the response rate remains limited due to the heterogeneity of HCC samples. Molecular subtypes of HCC vary in genomic background, clinical features, and prognosis. This study aims to compare the immune profiles between HCC subtypes and find subtype-specific immune characteristics that might contribute to the prognosis and potential of immunotherapy. The immune profiles consist of immune-related genes, cytolytic activity, immune pathways, and tumor-infiltrating lymphocytes. HCC-c1 samples showed an overall higher activation level of immune genes and pathways, and this pattern was consistent in validation sets. We associated the difference in immune profiles with the activation level of cancer hallmarks and genomic mutations. There was a negative correlation between most of the metabolism pathway and immune-related pathways in HCC samples. CTNNB1/WNT signaling pathway mutation, one of the common mutations in HCC, appears to be associated with the expression of immune genes as well. These results reveal the difference of immune profiles between HCC subtypes and possible reasons and influence, which may also deepen our understanding of the carcinogenesis process.