As both tumour mutational burden and TME have important implications in the response to immunotherapy46,47, higher total mutational burden, neoantigens loads as well as higher frequency of exhausted PD-1+CD8+ T cells (prime target for anti-PD-1 ICB) in HCC tumours with high immune-ITH could potentially show better respond to immunotherapy. Here, CD8A is linked to hepatocellular carcinoma.