Immunotherapy for Liver Cancer

Learn how immunotherapy is helping treat liver cancer

What Is Liver Cancer?

Liver cancer is the seventh-most commonly diagnosed cancer and the third leading cause of cancer death worldwide. In 2024, approximately 843,000 people were diagnosed with liver cancer, and about 732,000 died from the disease. In the U.S., an estimated 42,340 new cases and 30,980 deaths are expected in 2026.

The liver is a large organ in the upper right side of your abdomen, beneath the ribs. It processes nutrients, removes harmful substances from the blood, and makes bile, a fluid that helps digest body fats. 

Cancer that begins in your liver is called primary liver cancer. This is different from cancer that starts somewhere else in your body and spreads to your liver, which is called metastatic cancer, and is treated based on where it started.

There are three main types of primary liver cancer:

• Hepatocellular carcinoma (HCC) begins in hepatocytes, the main type of liver cell, and is the most common liver cancer in adults. It often develops in people who already have long-term liver disease.
• Intrahepatic cholangiocarcinoma begins in the bile ducts, which are small tubes that carry bile out of the liver. Although intrahepatic cholangiocarcinoma starts within the liver, it is actually a type of bile duct cancer and is treated differently from HCC.
• Rare liver cancers include fibrolamellar carcinoma, which often affects adolescents and young adults; angiosarcoma, which begins in cells that line blood vessels; and hepatoblastoma, which usually occurs in young children.

There is no single cause of liver cancer. Factors that can increase the risk of HCC include long-term hepatitis B or C infection, cirrhosis (scarring of the liver), heavy alcohol use, smoking, excess body weight, type 2 diabetes, and certain hereditary liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), which causes fat to build up in the liver, can also increase risk, particularly when it causes more serious liver damage or cirrhosis.

Getting the hepatitis B vaccine and treatment for hepatitis B or C, avoiding tobacco and alcohol, and maintaining a healthy weight can help lower liver cancer risk.

When liver cancer is found early and before it spreads, the five-year relative survival rate is about 37%. Once the cancer has spread to nearby tissues or lymph nodes, five-year survival drops to about 13%, and to about 4% when it reaches distant parts of the body (metastatic disease).

However, treatment options are improving: immunotherapy combinations have become important treatments for many people with advanced HCC. In April 2025, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) with ipilimumab (Yervoy®) as a first treatment for adults whose HCC cannot be removed by surgery or has spread.

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Is There Screening for Liver Cancer, and How Is It Diagnosed?

There is currently no routine liver cancer screening recommended for people at average risk or without known risk factors. 

Regular screening is recommended for people at higher risk of developing HCC, including many people with cirrhosis, chronic hepatitis B, and some hereditary liver diseases, such as hereditary hemochromatosis. Regular screening commonly includes an ultrasound of the liver and an alpha-fetoprotein (AFP) blood test about every six months.

Talk with your health care team about your risk and whether regular liver cancer screening is appropriate.

After a diagnosis, your health care team will also assess liver function and may test for hepatitis B or C. AFP levels may help with treatment planning and follow-up. 

Unlike some other cancers, most standard HCC treatments are not selected based on a particular tumor mutation. In some situations, however, biomarker testing may identify additional treatment options or help determine eligibility for a clinical trial.

What Are the Symptoms of Liver Cancer?

Liver cancer can be difficult to detect early because it may not cause symptoms at first, or its symptoms may resemble those caused by other more common conditions.

Possible symptoms include:

• Pain in the upper right abdomen, back, or near the right shoulder blade
• A lump or feeling of fullness beneath the ribs on the right side
• Unexplained weight loss
• Loss of appetite or feeling full after a small amount
• Nausea or vomiting
• Yellowing of the skin or whites of the eyes (jaundice)
• Dark urine or pale stools
• Fatigue or weakness
• Swelling in the abdomen
• Unusual bruising or bleeding

Having these symptoms does not necessarily mean you have liver cancer, but if symptoms are new, persistent, or getting worse, talk to your health care team.

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Can Liver Cancer Be Prevented?

Not all liver cancers can be prevented, but knowing your personal and family history can help you understand your risk.

Ways to help reduce liver cancer risk include:

• Get vaccinated against hepatitis B. The hepatitis B vaccine helps prevent infection and the liver cancer it can cause. There is currently no vaccine for hepatitis C.
• Get tested and treated for hepatitis when appropriate. Hepatitis B and C can be present without symptoms. Treatment can reduce liver damage and lower cancer risk, although some people still need regular liver cancer screening even after treatment.
• Avoid tobacco. Smoking is associated with an increased risk of liver cancer.
• Avoid or limit alcohol. Heavy alcohol use can damage the liver and lead to cirrhosis.
• Work toward a healthy weight and manage metabolic conditions. Excess body weight, type 2 diabetes, and MASLD can contribute to liver damage and increase liver cancer risk.
• Ask whether you need regular liver cancer screening. If you have cirrhosis, chronic hepatitis B, or another condition that puts you at higher risk, your health care team can recommend an appropriate screening plan to regularly monitor your liver health.

How Is Liver Cancer Treated?

Treatment for liver cancer depends on the type and stage of the cancer, how well the liver is working, and a patient’s overall health. 

For some people with early HCC, treatments intended to eliminate cancer include:

• Surgery to remove the abnormal part of the liver (the tumor)
• A liver transplant
• Or ablation, which destroys the cancer cells with heat or other methods. 

Other treatments may target tumors within the liver without surgery. These include radiation and treatments delivered through the blood vessels that supply the tumor, such as chemoembolization or radioembolization.

For advanced or recurrent disease that cannot be removed with surgery or has spread outside the liver, systemic treatments that travel throughout the body play an important role. These may include immunotherapy combinations or targeted therapies.

After initial treatment, regular follow-up is important to look for signs that the cancer has returned and to monitor liver health. Follow-up may include imaging, AFP testing, and liver function tests. People with hepatitis B or C may also need ongoing antiviral treatment.

Immunotherapies Used to Treat Liver Cancer

Immunotherapy is a type of cancer treatment that uses your immune system to recognize and attack cancer cells. It can help your immune cells overcome cancer’s defenses so they can better identify and fight the disease.

Immunotherapy has become an important treatment for many people with HCC that cannot be removed by surgery or has spread. The main immunotherapies approved specifically for HCC are immune checkpoint inhibitors (ICIs).

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors block immune checkpoints, such as PD-1, PD-L1, or CTLA-4, that cancer can use to suppress an immune response. Blocking these signals releases a natural “brake” on your immune system, allowing immune cells to respond more effectively to cancer.

• Atezolizumab (Tecentriq®) + bevacizumab (Avastin®): Approved as a first systemic treatment for patients with HCC that cannot be removed by surgery or has spread. Atezolizumab blocks the PD-L1 immune checkpoint. Bevacizumab is a targeted antibody that blocks VEGF, a protein that helps tumors grow new blood vessels.
• Durvalumab (Imfinzi®) + tremelimumab (Imjudo®): Approved for patients with HCC that cannot be removed by surgery. This combination is commonly used as a first systemic treatment. Durvalumab blocks PD-L1, and tremelimumab blocks CTLA-4.
• Nivolumab (Opdivo®) + ipilimumab (Yervoy®): Approved as a first treatment for patients with HCC that cannot be removed by surgery or has spread. Nivolumab blocks PD-1, and ipilimumab blocks CTLA-4.
• Pembrolizumab (Keytruda®): Approved for patients with HCC caused by hepatitis B who have already received systemic treatment that did not include a PD-1 or PD-L1 inhibitor. Pembrolizumab is also approved across cancer types for certain tumors with specific biomarkers, including some liver cancers. It blocks the PD-1 immune checkpoint.
• Dostarlimab (Jemperli®): Approved across cancer types for certain mismatch repair deficient (dMMR) tumors, which may include certain liver cancers. It blocks the PD-1 immune checkpoint.

Targeted Therapies Used to Treat Liver Cancer

Targeted therapies act on specific proteins or pathways that cancer cells use to grow and survive. Some also help the immune system recognize and destroy cancer cells. Biomarker testing can help identify whether one of these treatments may be appropriate.

Kinase Inhibitors

Kinase inhibitors block proteins that help cancer cells grow or help tumors form new blood vessels. These oral medicines may be used when immunotherapy is not appropriate or when additional treatment is needed.

• Lenvatinib (Lenvima®): Approved as a first-line treatment for patients with HCC that cannot be removed by surgery. Lenvatinib blocks several proteins involved in cancer growth and the formation of new blood vessels.
• Sorafenib (Nexavar®): Approved for patients with HCC that cannot be removed by surgery. Sorafenib blocks several proteins involved in cancer growth and the formation of new blood vessels.
• Cabozantinib (Cabometyx®): Approved for patients with HCC who have already received sorafenib. Cabozantinib blocks several proteins involved in cancer growth and the formation of new blood vessels.
• Regorafenib (Stivarga®): Approved for patients with HCC who have already received sorafenib. Regorafenib blocks several proteins involved in cancer growth and the formation of new blood vessels.

Antibody-Based Therapies

Some targeted treatments use antibodies to recognize specific proteins on cancer cells or interfere with signals that help tumors grow.

• Bevacizumab: Approved with atezolizumab as a first-line systemic treatment for patients with HCC that cannot be removed by surgery or has spread. Bevacizumab is a monoclonal antibody that blocks VEGF, a protein that helps tumors grow new blood vessels.
• Ramucirumab (Cyramza®): Approved for patients with HCC who have already received sorafenib and have high AFP blood levels. Ramucirumab is a monoclonal antibody that blocks VEGFR-2, a receptor involved in the growth of new blood vessels.

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Are There Immunotherapy Clinical Trials for Patients with Liver Cancer?

Yes. Clinical trials are carefully monitored research studies that test new treatments or new ways of using existing treatments. They may be available at any stage of liver cancer treatment, not only after standard options have stopped working.

Researchers are studying several types of immunotherapy in liver cancer clinical trials, including approaches designed to help more people respond to treatment, overcome resistance, and improve options for less common forms of liver cancer:

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How Is CRI Advancing Liver Cancer Research?

For more than 70 years, the Cancer Research Institute (CRI) has supported scientists studying liver cancer and the chronic inflammation that can lead to it. This research has helped scientists better understand how liver tumors interact with the immune system and identify new approaches for immunotherapy.

CRI-funded research has contributed to important discoveries about liver cancer biology. CRI investigator Gabriel A. Rabinovich, PhD, then at the University of Buenos Aires, Buenos Aires, showed how the protein galectin-1 can influence liver tumor growth, pointing to a possible treatment target. CRI Postdoctoral Fellow Zhenyu Zhong, PhD, then at the University of California, San Diego, identified a regulator of liver inflammation and developed an approach that prevented cancer-promoting inflammation in mice.

Today, CRI-funded scientists are exploring new ways to strengthen immune responses against liver cancer and overcome treatment resistance, including:

• CRI Irvington Postdoctoral Fellow Katherine Lindblad, PhD, at Boston Children’s Hospital, is studying dendritic cells, a type of immune cell that helps direct T cells toward cancer. Her research explores whether a highly active state of these cells can strengthen protective immune responses against HCC and inform new cell-based immunotherapies.
• CRI Irvington Postdoctoral Fellow Ondrej Belan, PhD, at Brigham and Women’s Hospital, is studying how proteins produced by viruses may help liver tumors hide from the immune system. His research uses laboratory models to test whether disrupting these signals can restore immune recognition and slow tumor growth.
• CRI Irvington Postdoctoral Fellow Jing Zhang, PhD, at Memorial Sloan Kettering Cancer Center, is studying how a type of immune cell called an innate lymphoid cell may help fight liver cancer. Her research combines immune checkpoint blockade with an immune-stimulating protein and is investigating whether the approach could strengthen lasting immune protection.
• CRI Clinical Innovator Marina Baretti, MD, at Johns Hopkins University School of Medicine, is investigating whether changing how tumor cells use a nutrient called glutamine can help immunotherapy work better against fibrolamellar carcinoma. Her project combines the experimental drug DRP-104 with durvalumab and studies patient samples to understand how the treatment affects cancer and immune cells.