Abstract:

The application of immune checkpoint inhibitors (ICB) has led to significant advances in systemic therapy for advanced hepatocellular carcinoma (HCC). The systemic treatment of cancer has experienced tremendous paradigm towards targeting tumor microenvironment (TME). However, the efficacy of ICB therapy alone is limited, and combining immunotherapy with current treatment strategies may yield better results. Radiotherapy (RT) is an integral part of solid cancer therapy including HCC. Stereotactic body radiotherapy (SBRT) has been used to treat primary HCC for the past ten years and has achieved good results. High dose radiotherapy is more likely to produce abscopal effects, suggesting its potential role in immune activation. The combination of immunotherapy and radiotherapy may be a promising strategy for synergistically enhancing efficacy. Radiation induced cancer cell damage exposes tumor-specific antigens that are visible under immune surveillance and promotes the initiation and activation of cytotoxic T cells. Radiation induced tumor microenvironmental regulation may also promote the recruitment and infiltration of immune cells. The efficacy of RT combined with ICB has also been demonstrated in some clinical studies. But there are still unsolved challenges to make the most appropriate combination strategy. Here, we summarize the advances in combination therapy of RT and ICB in HCC, the mechanisms by which radiotherapy and the immune system work together, and discuss the challenges of current radiotherapy and immune checkpoint blocking therapies and possible strategies to enhance this combination in the future.

Key words: Radiotherapy, Immunotherapy, Tumor immune microenvironment, Immune checkpoints, Combination therapy