Immunotherapy
For Liver Cancer

How is Immunotherapy for Liver Cancer Changing the Outlook for Patients?

Reviewed by:

Ignacio Melero, MD, PhD
Foundation for Applied Medical Research (FIMA, Spain)

Immunotherapy for liver cancer can enhance cancer-fighting immune system responses, but may not always be available or viable for patients with a history of hepatitis infection.

The liver performs many vital functions involved in detoxification, drug processing, and metabolism of fat and sugars. Cancers of the liver often spread to other organs, such as the breasts or lungs. Approximately 80% of liver cancers start in a type of liver cell called the hepatocytes. The majority of other liver cancers arise from cells of the bile ducts. Types of liver cancer include:

• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma (bile duct cancer)
• Hepatoblastoma, the most common type of childhood liver cancer

A major cause of liver cancer is the hepatitis virus, which is responsible for roughly 80% of all cases. Inflammation in liver, resulting from untreated hepatitis B and hepatitis C, can lead to scarring (cirrhosis). As the liver attempts to repair and replace the damaged tissue, there is a greater chance for error in DNA replication, which can lead to cancer.

Fortunately, it is possible to prevent hepatitis via vaccination; the hepatitis B vaccine (below) was the first preventive cancer vaccine developed (in 1982). While there is currently no vaccine to prevent hepatitis C virus (HCV) infection, there are direct-acting antivirals that seem to be effective at reducing the incidence of liver cancer.

Preventive Vaccine

• Hepatitis B (HBV) vaccine (HEPLISAV-B®): a preventive cancer vaccine that protects against infection by the hepatitis B virus; can help prevent the development of HBV-related liver cancer

Other risk factors for liver cancer include alcohol-related cirrhosis, obesity, and diabetes.

More men than women are diagnosed with liver cancer, although rates of liver cancer appear to be on the rise in both. Globally, in 2018, there were an estimated 840,000 new cases of liver cancer along with 780,000 deaths. In the United States alone, 41,000 people new cases of liver cancer will be diagnosed in 2023, and roughly 29,000 will die from the disease. The overall 5-year relative survival rate for patients with liver cancer is 17%. Less than half of patients with liver cancer are diagnosed at an early stage, when the 5-year survival is 31%. For patients with regional and metastatic disease, survival rates drop to 11% and 3%, respectively. 

Since the human body cannot survive without a functioning liver, this cancer presents an urgent need for more effective treatments.

Liver Cancer Treatment Options

Standard liver cancer treatments include surveillance, surgery, liver transplant, ablation therapy, embolization therapy, targeted therapy, and radiation therapy. For advanced HCC, the standard of care is the immunotherapy combination of the checkpoint inhibitor atezolizumab and the targeted antibody bevacizumab.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently six FDA-approved immunotherapy options for liver cancer.

Immunomodulators

• Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-L1 pathway; approved, in combination with bevacizumab, as a first-line treatment for subsets of patients with advanced liver cancer
• Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced liver cancer that has DNA mismatch repair deficiency (dMMR)
• Durvalumab (Imfinzi®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved in combination with tremelimumab for subsets of patients with unresectable liver cancer
• Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved, in combination with nivolumab, for patients with advanced, previously treated liver cancer
• Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced liver cancer, including in combination with ipilimumab
• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced liver cancer, including those with high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)
• Tremelimumab (Imjudo®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved in combination with durvalumab for subsets of patients with unresectable liver cancer

Targeted Antibodies

• Bevacizumab (Avastin®): a targeted antibody that targets the VEGF-A pathway; approved, in combination with atezolizumab, as a first-line treatment for subsets of patients with advanced liver cancer

Immunotherapy treatments can enhance cancer-fighting immune system responses, but may not always be available or viable for patients with a history of hepatitis infection, as this type of immune system activity can damage normal, functioning liver cells.

Several other immunotherapies are currently being tested in clinical trials, including oncolytic viruses and adoptive cell therapy.

CRI’s Impact in Liver Cancer

At the Cancer Research Institute, we’re dedicated to supporting scientific research for liver cancer, working to advance immunotherapy as a viable treatment for people affected by this disease. The scientists we fund have studied liver cancer—and the chronic inflammation from hepatitis B and hepatitis C viruses that causes it—for more than 30 years.

• Gabriel A. Rabinovich, PhD, a CRI investigator from 2006-2010 at the University of Buenos Aires, Buenos Aires, Argentina, provided the first demonstration that galectin-1 plays a role in modulating cell adhesion and tumor growth in liver cancer, suggesting that it could be a promising target to prevent or slow liver cancer progression.
• Paul Klenerman, MD, PhD, a Clinic and Laboratory Integration Program (CLIP) grantee from 2014-2016 and a professor at the University of Oxford, United Kingdom, studied a novel set of immune cells called mucosal-associated invariant T (MAIT) cells and their association with inflammation as a cause of liver cancer.
• In 2013, Thomas Chia Ting Fung, a graduate student at the University of Pennsylvania School of Medicine, was awarded a STaRT grant to study the role of innate lymphoid cell-controlled intestinal barrier function in hepatocellular carcinoma.
• Zhenyu Zhong, PhD, a postdoctoral fellow at the University of California, San Diego from 2014-2017, identified a key regulator of liver inflammation that appears to play a role in obesity-associated liver cancer. He also developed a strategy capable of preventing this cancer-promoting inflammation in mice.
• The CRI Anna-Maria Kellen Clinical Accelerator is funding a clinical study that seeks to determine the effectiveness of combining the CTLA-4 inhibitor tremelimumab with the PD-L1 inhibitor durvalumab in patients diagnosed with various advanced solid tumors who have failed standard therapy.

Explore CRI’s current funding for liver cancer research in our funding directory.