Radiation and immune checkpoint inhibitors: Combination therapy for treatment of hepatocellular carcinoma Review


Authors: Chami, P.; Diab, Y.; Khalil, D. N.; Azhari, H.; Jarnagin, W. R.; Abou-Alfa, G. K.; Harding, J. J.; Hajj, J.; Ma, J.; El Homsi, M.; Reyngold, M.; Crane, C.; Hajj, C.
Review Title: Radiation and immune checkpoint inhibitors: Combination therapy for treatment of hepatocellular carcinoma
Abstract: 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. © 2023 by the authors.
Keywords: hepatocellular carcinoma; liver cell carcinoma; multimodality cancer therapy; carcinoma, hepatocellular; liver neoplasms; combined modality therapy; immunotherapy; liver tumor; radiation therapy; combination therapy; tumor microenvironment; immune checkpoint inhibitor; humans; human; immune checkpoint inhibitors
Journal Title: International Journal of Molecular Sciences
Volume: 24
Issue: 23
ISSN: 1422-0067
Publisher: MDPI  
Date Published: 2023-12-01
Start Page: 16773
Language: English
DOI: 10.3390/ijms242316773
PUBMED: 38069095
PROVIDER: scopus
PMCID: PMC10706661
DOI/URL:
Notes: Review -- MSK corresponding author is Carla Hajj -- Source: Scopus
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MSK Authors
  1. James Joseph Harding
    250 Harding
  2. Ghassan Abou-Alfa
    569 Abou-Alfa
  3. William R Jarnagin
    903 Jarnagin
  4. Marsha Reyngold
    103 Reyngold
  5. Carla Hajj
    164 Hajj
  6. Danny Nejad Khalil
    64 Khalil
  7. Jennifer Ma
    74 Ma
  8. Christopher   Crane
    202 Crane
  9. Hassan Azhari
    3 Azhari