Programmed Death Ligand 1 (PD-L1) and Tumor-Associated Macrophages in Gastric-Type Hepatocellular Carcinoma: Prognostic Insights

Hepatocellular carcinoma (HCC) is a heterogeneous primary liver malignancy characterized by limited treatment options and low overall survival rates. Recent studies have explored the role of programmed death ligand 1 (PD-L1), tumor-associated macrophages (TAMs), and epithelial-mesenchymal transition (EMT) in modulating tumor progression and the response to immunotherapy. This study aimed to investigate the association among PD-L1 expression, TAMs, and EMT in HCC, highlighting the recently proposed immunophenotypic variant—gastric-type HCCs. A retrospective cohort of 50 surgically resected HCC patients was analyzed. Immunohistochemical staining was performed for PD-L1 (clones 28-8 and 22C3), CD68 (TAMs), and EMT markers (VSIG-1, TTF-1, and vimentin). PD-L1 expression was detected in 52% of the patients and was significantly associated with high TAM counts (p < 0.001). Compared with PD-L1-negative patients, those with gastric-type HCCs, which are characterized by VSIG-1 and TTF-1 co-expression and vimentin negativity, demonstrated improved survival outcomes (p = 0.03). Integration of immune and EMT profiling of tumor cells in routine diagnostics may guide prognosis and immunotherapeutic strategies in HCC. Further molecular validation is required to confirm the biological significance of the proposed gastric-type HCC immunophenotype.