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While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.

Identification of immune landscape signatures associated with clinical and prognostic features of hepatocellular carcinoma