Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2416
Peer-review started: February 22, 2019
First decision: March 27, 2019
Revised: April 12, 2019
Accepted: April 19, 2019
Article in press: April 19, 2019
Published online: May 28, 2019
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes; therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment.
Core tip: In the era of cancer immunotherapy, the roles of radiation therapy (RT) are not limited to the direct killing of cancerous cells but have expanded to immune modulation. Numerous proof-of-concept preclinical studies have proven that combination approaches of RT and immune checkpoint inhibitors (ICIs) are highly promising for many types of cancers, and currently, many related clinical trials are ongoing. Historically, RT was considered ineffective for hepatocellular carcinoma (HCC), but the efficacy of RT in HCC has improved greatly with technical advances. Our goal of this review is to provide a rationale for the combined treatment with RT and ICIs in HCC.