The role of peritumoral CD8 + /TIA1 + lymphocytes in hepatocellular carcinoma aggressiveness and recurrence after surgical resection

Hepatocellular carcinoma (HCC) is characterized by a low mutation burden and a relatively low number of tumor-infiltrating lymphocytes (TILs), making still difficult to identify targets for specific therapies. The aim of this study was the identification of the prognostic role of TILs in HCC, focusing on their distribution and status of activation. We retrospectively enrolled 41 patients, undergone to liver resection for HCC. A significant increase of CD8 + intratumoral lymphocytes was observed in HCCs with prevalent solid architecture, but with a higher PD-1/TIA1 ratio, suggesting that HCCs with solid architecture have more peri-tumoral lymphocytes, but with minor functionality. At multivariate and univariate analyses, TIA1/CD8 ratio correlated with tumor recurrence, meaning that HCC with more activated TILs are characterized by a higher tumor aggressiveness. The use of a feasible and cheap immunohistochemical panel can help in post-surgical prognostic stratification, focusing not only in the raw number and density of TILs, but more on their state of activation and morphology.