Characterization of the Immune Microenvironment in Hepatocellular Carcinoma (HCC)

Purpose: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. Experimental Design: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. Results: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24/29 cases (83%) and positive expression of LAG-3 on tumor infiltrating lymphocytes was identified in 19/29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted. Conclusions: LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC.

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