Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma

Perla Chami, Youssef Diab, Danny N. Khalil, Hassan Azhari, William R. Jarnagin, Ghassan K. Abou-Alfa, James J. Harding, Joseph Hajj, Jennifer Ma, Maria El Homsi, Marsha Reyngold, Christopher Crane, Carla Hajj

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


The liver tumor immune microenvironment has been thought to possess a critical role in the development and progression of hepatocellular carcinoma (HCC). Despite the approval of immune checkpoint inhibitors (ICIs), such as programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, for several types of cancers, including HCC, liver metastases have shown evidence of resistance or poor response to immunotherapies. Radiation therapy (RT) has displayed evidence of immunosuppressive effects through the upregulation of immune checkpoint molecules post-treatment. However, it was revealed that the limitations of ICIs can be overcome through the use of RT, as it can reshape the liver immune microenvironment. Moreover, ICIs are able to overcome the RT-induced inhibitory signals, effectively restoring anti-tumor activity. Owing to the synergetic effect believed to arise from the combination of ICIs with RT, several clinical trials are currently ongoing to assess the efficacy and safety of this treatment for patients with HCC.

Original languageEnglish
Article number16773
JournalInternational Journal of Molecular Sciences
Issue number23
StatePublished - Dec 2023
Externally publishedYes


  • combination therapy
  • hepatocellular carcinoma
  • immune checkpoint inhibitors
  • immunotherapy
  • radiation therapy


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