Tertiary lymphoid structures and hepatocellular carcinoma: Guardian and executioner

Tertiary lymphoid structures (TLS) are essential immune components within the tumor microenvironment. The cellular composition, heterogeneity, and maturity of TLS are closely associated with tumor progression, response to therapy, and patient prognosis. Although numerous studies have highlighted the antitumor potential of TLS, their role can vary-either inhibiting or promoting tumor growth-depending on the specific microenvironment or disease stage. Hepatocellular carcinoma (HCC), the most common and aggressive primary liver cancer, frequently resists immune checkpoint therapy. In this context, inducing antitumor TLS has emerged as a key strategy to remodel the immune microenvironment, overcome drug resistance, and enhance the effectiveness of HCC immunotherapy. This review outlines the cellular composition and formation process of TLS, compares TLS in liver cancer with those in other cancer types, and explores their roles in HCC pathogenesis, progression, and treatment. These findings are expected to provide novel therapeutic strategies for enhancing the efficacy of immunotherapy in liver cancer.