Expression of Poliovirus Receptor, the Ligand of TIGIT, Associated With Immune-Cold Tumor Microenvironment in Hepatocellular Carcinoma

PURPOSE Targeting TIGIT is under investigation in various cancers. We explored the expression and clinical significance of the poliovirus receptor (PVR), the ligand of TIGIT, in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). PATIENTS AND METHODS Two groups of patients with HCC, those with metastatic and early-stage disease, were identified at a single medical center. The expression levels of PVR and PD-L1 in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) were evaluated by immunohistochemistry for membranous staining. Immune gene expression profiling and data from The Cancer Genome Atlas (TCGA) were used for validation. RESULTS Among 66 metastatic HCC tissues, 13 (19.7%) and 18 (27.3%) exhibited positive PVR expression and 17 (25.8%) and 36 (54.5%) exhibited positive PD-L1 expression in TCs and ICs, respectively. In both TCs and ICs, the intensities of PVR and PD-L1 expression were negatively correlated. Immune profiling of representative tumor specimens revealed that those with high PVR/low PD-L1 expressions had significantly lower CD8 + T-cell scores, cytotoxic cell scores, and CD8 + /regulatory T-cell score ratios compared with those with high PD-L1/low PVR expressions. In the other group of 90 early-stage hepatectomy HCC tissues, the expression levels of PVR and PD-L1 were lower than those in metastatic HCC tissues. The inverse correlation between PVR and PD-L1 expression, and the association between PVR expression and low infiltration of CD8 + T cells or cytotoxic cells were also demonstrated in early-stage HCC tissues and supported by the TCGA data set. CONCLUSION HCC tissues with high PVR expression were more common in metastatic disease and were associated with an immune-cold TME. These findings may have implications for the development of immunotherapies for HCC.