Pathological study of the tumor microenvironment after neoadjuvant therapy in hepatocellular carcinoma: Difference of TACE combined with antiangiogenics and immunotherapy

Background: HCC is the leading form of primary liver cancer worldwide. Transcatheter arterial chemoembolization (T) is commonly used to treat unresectable tumors. T combined with antiangiogenic therapy and immunotherapy (AI) has shown significant progress in neoadjuvant treatment, although the underlying mechanisms remain unclear. This study aimed to explore the reasons for the enhanced efficacy of T+AI from a pathological perspective in the context of HCC. Methods: A retrospective analysis was conducted on 49 patients with HCC who were treated with T before surgical resection. Twenty-three patients received T+AI, while 26 received only T. Immunohistochemistry was performed to evaluate clinical data, including disease-free survival. Immune cells were recorded based on 4 methods, including tumor-infiltrating lymphocyte (TIL) percentage (the percentage of positive lymphocytes in the central area of the tumor) and the other 3 methods. Blood vessels were classified on the basis of the presence of VETC (vessels that encapsulate tumor clusters). Results: The group analysis results suggested that disease-free survival in the T+AI group was significantly better than that in the T group. Analysis revealed that CD8+TILs were a prognostic factor for neoadjuvant treatment and lower carbonic anhydrase 9 and VETC positivity in the T+AI group, with significant differences in immune cell infiltration and vascular classification. VETC positivity was associated with higher residual tumor rates and lower CD8+TIL levels. Conclusions: Pathological assessment of CD8+TILs in cancer tissues may serve as an important indicator for evaluating the efficacy of neoadjuvant therapy in HCC. The presence of VETC and carbonic anhydrase 9 may also affect the efficacy of neoadjuvant therapy and could potentially serve as indicators.