Radiotherapy and Immunotherapy In Hepatocellular Carcinoma: Priming the Tumor Immune Microenvironment From Bench To Bedside.

Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of mortality from cancer worldwide. Surgical resection is the main curative strategy for early-stage HCC; however, many advanced cases require multidisciplinary management, including radiotherapy and immunotherapy. Recent advances in radiation delivery have enabled precise tumor targeting while sparing healthy liver tissue, thereby expanding the role of radiotherapy beyond palliation. Moreover, the intricate effect of radiotherapy on the tumor microenvironment (TME) is being increasingly understood. In this review, we systematically examine the bidirectional immunomodulatory effects of radiotherapy on the TME and the biological rationale for combining radiotherapy with immunotherapy in HCC. We also summarize the preclinical and clinical evidence supporting radiotherapy-immunotherapy combinations in HCC and discuss future directions. Continued translational and clinical research is necessary to fully realize the therapeutic potential of this strategy in HCC management.