Angiogenesis and Immunosuppressive Niche in Hepatocellular Carcinoma: Reshaping Vascular - Immune Axis to Potentiate antiPD - 1/PD - L1 Therapy.

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related death worldwide, and its complex tumor microenvironment (TME) presents significant challenges for the treatment of this disease. In recent years, tumor immunotherapy has emerged as one of the most successful strategies in cancer treatment, especially for advanced HCC. Programmed cell death protein-1 (PD-1) inhibitors have moderate efficacy as monotherapies for HCC. Tumor angiogenesis, a crucial factor in tumor growth and proliferation, plays a pivotal role in the immune regulation of HCC. The vascular and immune microenvironments of solid tumors engage in dynamic reciprocal crosstalk, forming a complex vascular-immune axis that critically shapes antitumor immune responses and drives therapy resistance. The high degree of angiogenesis observed in HCC leads to abnormal vascular structure and function, which not only promotes tumor growth but also induces hypoxia and acidosis within the TME, thereby suppressing the immune response through various mechanisms. Given the regulatory role of tumor blood vessels in the immune system, the integration of antiangiogenic therapy into current immunotherapy approaches provides a novel treatment option. This integration involves the inhibition of tumor angiogenesis, improvements in the TME, and enhancements of the immune response, among other mechanisms. This review summarizes the angiogenic mechanisms of HCC, the clinical applications of immunotherapy and the regulatory effects of angiogenesis on the immune response in HCC.