The regulatory effects and applications of TIGIT/CD155 on the tumor microenvironment in HCC

Abstract Hepatocellular carcinoma (HCC) is the most commonly occurring liver cancer, and poses a significant burden on individuals, society, the economy, and the healthcare system. Despite advancements in therapeutic options such as surgical interventions and targeted therapies, the complex etiology and clinical presentations of liver cancer continue to result in suboptimal treatment responses. Therefore, identifying more effective treatment methods has become a priority in HCC research. Targeting programmed cell death protein 1 with immune checkpoint inhibitors has significantly improved cancer treatment outcomes; however, these drugs are still limited by their suboptimal efficacy and risk of immune‐related adverse reactions, which can result in death. TIGIT, a newly emerging immune checkpoint, provides a novel focus for immunotherapy. The TIGIT/CD155 axis actively reprograms the tumor microenvironment (TME), driving carcinogenesis, immune evasion, and metastatic spread. This review systematically elucidates the dynamic regulatory networks and biological impacts of the TIGIT/CD155 axis in the HCC TME, while evaluating its therapeutic potential through two exploratory strategies: (i) TIGIT inhibitors have the potential to augment the anticancer efficacy of PD‐1/PD‐L1 blockade, and (ii) combination regimens integrating TIGIT‐targeted therapies with antibody–drug conjugates (ADCs) or chimeric antigen receptor macrophages (CAR‐Ms) could represent a viable approach to overcoming the efficacy limitations inherent to monotherapy.