PD-L1, CD8 + T-cell density, and CD105 angiogenesis: insights into the tumor microenvironment of hepatocellular carcinoma

Abstract Background and objectives Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The programmed death ligand 1 (PD-L1) immune checkpoint suppresses antitumor immunity in various malignancies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factors β (TGF-β) co-receptors. Involvement of that protein in angiogenesis of solid tumors is well documented. There is an important role of CD8 + tumor infiltrating lymphocytes in host immune defense against tumor progression. Our study aims to evaluate the expression of PD-L1, CD105 &CD8 in HCC and to correlate it with the clinicopathological parameters. Material and methods Sixty paraffin-embedded resection HCC cases were evaluated immunohistochemically for PD-L1, CD105 &CD8 expressions. Results Out of sixty cases studied, PD-L1 was positively expressed in 55 cases, 48.3% scoring 3, 43.3% scoring 2. Only a small subset exhibited absent (3.3%) or weak (5.0%) expression. The intra-tumoral CD8 + T-cell infiltration showed a wide distribution, with a mean value of 36.53 ± 35.45. Peri-tumoral CD8 + cell density also showed substantial variability (mean = 51.98 ± 30.58), with a median of 46.5 used as the cutoff threshold. CD105 micro vessel density, had a mean of 29.40 ± 12.83 and a median cutoff of 27.0, with moderate skewness (1.104). A significant positive correlation was found between intra-tumoral and peri-tumoral CD8 + T-cell infiltration (r = 0.264, p = 0.042). Moreover, CD8 peri-tumoral infiltration was moderately correlated with CD105 expression (r = 0.348, p = 0.007). However, no significant correlations were observed between PD-L1 expression and any of the investigated immune markers or clinicopathological variables, including tumor size and patient age (all p > 0.05). Conclusions PD-L1, CD105 &CD8 expression in most of the studied HCC cases may evoke the potential therapeutic combination of anti PD-L1 & anti CD105 antibodies for this cancer. Immunotherapy, with recent pharmacologic achievement, is a new strategi in cancer therapy and so immunobiology of hepatocarcinogenesis is a novel trial.