Immune Checkpoint Inhibitors Combined with Radiotherapy for Hepatocellular Carcinoma

Early-stage Hepatocellular carcinoma (HCC) is usually treated with liver transplantation, surgical resection, ablation, or transarterial therapy. However, effective treatment options for patients with advanced diseases are still limited. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising treatment regimen for these patients. Although the application of ICIs has improved the survival and efficacy of patients with HCC, most of them fail to benefit from ICIs. How to enhance the anti-tumor effects of ICIs is under exploration. In recent years, the improvements in radiation techniques over the past two decades have improved the efficacy and safety of radiation therapy in HCC, such as stereotactic body radiation therapy (SBRT), allowing high doses of radiation to be delivered to the tumor while limiting damage to surrounding healthy tissue. In theory, radiotherapy-induced upregulation of immune checkpoint molecules/pathways could restore antitumor immunity. In addition, radiotherapy can also re-model originally “cold” TME into immunoreactive “hot” TME, thereby synergistically enhancing the effectiveness of ICIs. In preclinical studies, they have shown encouraging efficacies and tolerable toxicity profiles in cancer patients treated with the combination of radiotherapy and ICIs. However, more evidence is needed with regards to the actual effectiveness, the radiotherapy dose and fraction, the sequencing of radiotherapy, and the timing of radiotherapy. Meanwhile, with the increasing number of relevant clinical studies, the discovery of predictive biomarkers to identify potentially eligible patients who can benefit from this combination is also urgent. Despite the promising effects of ICIs in HCC, many issues remain unresolved. Specifically, the mechanism by which radiotherapy combined with ICIs controls disease; the toxicity profiles of radiotherapy combined with ICIs, and the optimal dose, fractionation regimen, and radiation sequence. In addition, the lack of reliable predictive biomarkers for HCC treatment (tumor burden, gene mutations, immune characteristics, inflammation, etc.) and the interaction pathways between radiotherapy and immunotherapy are also important to improve and understand the therapeutic efficacy of this combined strategy in HCC patients.

This Research Topic aims to publish studies on the efficacy and toxicity of immunotherapy combined with radiotherapy in the treatment of HCC, including preclinical and clinical studies. We welcome submissions of Original Research, Review, Clinical Trial, Opinion, and Perspective in this field but are not limited to:

1. New preclinical or clinical studies reporting the efficacy and safety of radiation combined with ICIs in the treatment of HCC
2. Discovery and validation of predictive biomarkers for efficacy and toxicity following the combination of radiation and ICIs in the treatment of HCC
3. Novel findings on the mechanism of the interaction between radiation and ICIs

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.