Immunosenescence and immunotherapy in elderly patients with hepatocellular carcinoma

Liver cancer, more specifically hepatocellular carcinoma (HCC), is a global health issue and one of the dominant causes of cancer death around the world. In the past few decades, remarkable advances have been achieved in the systemic therapy of HCC. Immune checkpoint inhibitors (ICIs) have become a therapy mainstay for advanced HCC and have shown promise in the neoadjuvant therapy before resection. Despite these significant advancements, the compositions and functions of the immune system occur various alterations with age, called "immunosenescence", which may affect the antitumor effects and safety of ICIs, thus raising concerns that immunosenescence may impair elderly patients' response to ICIs. Therefore, it is important to learn more about the immunosenescence characteristics of elderly patients. However, the real-world elderly HCC patients may be not accurately represented by the elderly patients included in the clinical trials, affecting the generalizability of the efficacy and safety profiles from the clinical trials to the real-world elderly patients. This review summarizes the characteristics of immunosenescence and its influence on HCC progression and immunotherapy efficacy as well as provides the latest progress in ICIs available for HCC and discusses their treatment efficacy and safety on elderly patients. In the future, more studies are needed to clarify the mechanisms of immunosenescence in HCC, and to find sensitive screening tools or biomarkers to identify the patients who may benefit from ICIs.