Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

<b>Purpose:</b> Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies.<b>Experimental Design:</b> To characterize the immune microenvironment in HCC, 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.<b>Results:</b> 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 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 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.<b>Conclusions:</b> 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. <i>Clin Cancer Res; 23(23); 7333-9. ©2017 AACR</i>.