Immunotherapy for Pancreatic Cancer

Learn how immunotherapy is used to treat certain pancreatic cancers

Can Immunotherapy Treat Pancreatic Cancer?

Yes, though immunotherapy is currently an option for only a small number of patients with pancreatic cancer. 

Most pancreatic cancers do not respond well to currently approved immunotherapies. This is partly because pancreatic tumors can create an environment that limits immune cell activity and makes it difficult for immune cells to reach and attack cancer cells.

However, certain pancreatic cancers have biomarkers, such as microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). Having these biomarkers makes cancer more likely to respond to immune checkpoint inhibitors, including pembrolizumab (Keytruda®) and dostarlimab (Jemperli®). Researchers are also studying new approaches, including cancer vaccines, cell therapies, and combinations with other treatments, to help more patients benefit from immunotherapy.

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What Is Pancreatic Cancer?

The pancreas is an organ behind the stomach that produces digestive juices to break down food and hormones, including insulin which helps control blood sugar. Pancreatic cancer develops when cells in the pancreas grow out of control. 

Pancreatic cancer is the 11th-most commonly diagnosed cancer worldwide and a leading cause of cancer death. In 2024, approximately 531,000 people were diagnosed with pancreatic cancer worldwide, and about 491,000 died from the disease. In the U.S., an estimated 67,530 new cases and 52,740 deaths are expected in 2026.

The main types of pancreatic cancer include:

• Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancers. It begins in the cells lining the pancreatic ducts, small tubes that carry digestive juices out of the pancreas.
• Other exocrine cancers, such as acinar cell carcinoma, are uncommon. They begin in the cells involved in producing digestive juices.
• Pancreatic neuroendocrine tumors (pNETs) are less common and begin in cells that produce hormones.

These cancers can behave differently and require different treatments, and the information below focuses primarily on PDAC.

There is no single cause of pancreatic cancer. Factors that can increase risk include older age, smoking, excess body weight, diabetes, long-term inflammation of the pancreas (chronic pancreatitis), family history, and certain hereditary genetic mutations.

Pancreatic cancer is often diagnosed after it has spread because it may not cause noticeable symptoms early on. When the cancer is found early, before it has spread beyond the pancreas, the five-year relative survival rate is ~44%. Survival decreases to ~17% when it has spread to nearby tissues or lymph nodes and 3% when it has spread to distant parts of the body (metastatic disease).

Although pancreatic cancer remains difficult to treat, researchers are developing new immunotherapies and studying ways to overcome the barriers that make pancreatic tumors resistant to immune attack.

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

There is currently no routine screening test recommended for pancreatic cancer in people at average risk or without known risk factors. Because the pancreas is located deep inside the abdomen, early pancreatic cancers are difficult to detect through a routine physical exam.

However, people with certain hereditary genetic mutations or a strong family history of pancreatic cancer may benefit from regular screening. About 10% of pancreatic cancers may be linked to mutations in genes such as BRCA1, BRCA2, PALB2, ATM, and those associated with Lynch syndrome. 

If pancreatic cancer or related cancers, such as breast, ovarian, prostate, colorectal, or melanoma, run in your family, talk with your health care team about whether genetic counseling or testing may be appropriate. For people at high risk, screening may include MRI scans or endoscopic ultrasound, which uses a thin tube passed through the mouth to take detailed images of the pancreas.

When pancreatic cancer is suspected, your health care team may use imaging tests, blood tests, and a physical exam to learn more. A diagnosis is confirmed by examining cells or tissue under a microscope. In some cases, surgery may be performed without a biopsy beforehand.

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What Are Genetic and Biomarker Testing?

Genetic and biomarker testing can help guide treatment and identify hereditary changes that may also be important for family members. Hereditary genetic testing, usually performed using blood or saliva, is recommended for everyone diagnosed with pancreatic cancer. Tumor testing examines features of the cancer itself and can help identify targeted therapies, immunotherapies, or clinical trials.

Testing may include:

What Are the Symptoms of Pancreatic Cancer?

Pancreatic cancer can be difficult to detect early because the disease may cause no symptoms at first. When symptoms develop, they can resemble those of more common conditions.

Possible symptoms include:

• Yellowing of the skin or whites of the eyes (jaundice), sometimes with itching
• Dark urine or pale, greasy stools
• Pain in the upper abdomen or back
• Unexplained weight loss or loss of appetite
• Nausea or vomiting
• New diabetes or diabetes that becomes harder to control
• Fatigue or weakness

If the cancer has spread beyond the pancreas, additional symptoms may develop, such as swelling in the abdomen from a buildup of fluid.

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

Can Pancreatic Cancer Be Prevented?

There is no guaranteed way to prevent pancreatic cancer, and many people who develop it have no known risk factors. However, certain steps may help lower your risk:

• Avoid tobacco. Smoking is one of the most important preventable risk factors for pancreatic cancer.
• Maintain a healthy weight and stay physically active. Excess body weight is associated with increased pancreatic cancer risk.
• Limit heavy alcohol use. Heavy drinking can contribute to chronic pancreatitis, which increases pancreatic cancer risk.
• Know your family history. Certain hereditary genetic mutations increase the risk of pancreatic cancer and other cancers. Genetic counseling may help you understand your risk.

How Is Pancreatic Cancer Treated?

Treatment for pancreatic cancer depends on the type and stage of the disease, whether the tumor can be removed with surgery, its genetic features, and the patient’s overall health. 

For pancreatic cancer that can be removed, treatment usually includes surgery and chemotherapy. Chemotherapy may be given before surgery to shrink the tumor or afterward to reduce the risk of recurrence. Radiation therapy may also be used in certain situations.

For advanced or recurrent disease, chemotherapy remains the primary treatment for many patients. Some patients may also benefit from targeted therapies or immunotherapy based on the genetic features of their cancer. After initial treatment, some patients may receive maintenance therapy to help keep the cancer from growing or returning.

Immunotherapies Used to Treat Pancreatic 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.

While immunotherapies are not yet effective for most pancreatic cancers, immune checkpoint inhibitors (ICIs) may benefit some patients whose tumors have specific biomarkers. 

Immune Checkpoint Inhibitors:

Immune checkpoint inhibitors are a type of immunotherapy that block signals, such as PD-1, PD-L1, or CTLA-4, that normally help regulate immune activity. Blocking these signals can help immune cells respond more effectively to cancer.

• Pembrolizumab (Keytruda®): Approved for patients with tumors that cannot be removed by surgery or have spread and are MSI-H, dMMR, or TMB-H. This treatment is used when cancer has progressed after prior therapy and there are no satisfactory alternatives. Pembrolizumab blocks the PD-1 immune checkpoint.
• Dostarlimab (Jemperli®): Approved for patients with recurrent or advanced dMMR tumors that have progressed after prior treatment and when there are no satisfactory alternatives. It blocks the PD-1 immune checkpoint.

Targeted Therapies Used to Treat Pancreatic Cancer

Targeted therapies act on specific genes, proteins, or pathways that cancer cells depend on. Unlike immunotherapy, which works through your immune system, these treatments target particular features of the cancer. Biomarker testing can help identify whether one of these treatments may be appropriate.

PARP Inhibitors:

PARP inhibitors block a protein that helps cells repair damaged DNA. Some pancreatic cancers with BRCA1 or BRCA2 gene mutations already have trouble repairing DNA, making them more vulnerable to these treatments.

• Olaparib (Lynparza®): Approved as maintenance therapy for patients with metastatic PDAC and a hereditary BRCA1 or BRCA2 gene mutation whose cancer has not progressed after at least 16 weeks of first-line platinum-based chemotherapy. 

Antibody-Based Therapies:

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

• Zenocutuzumab (Bizengri®): Approved for patients with advanced PDAC that cannot be removed by surgery or has spread, has an NRG1 gene fusion, and has progressed during or after prior systemic treatment. It is a bispecific antibody that binds the HER2 and HER3 proteins to block cancer growth signals.
• Trastuzumab deruxtecan (Enhertu®): Approved for adults with tumors that cannot be removed by surgery or have spread and have high levels of the HER2 protein, after prior treatment when there are no satisfactory alternatives. It is an antibody-drug conjugate that recognizes HER2 and delivers cancer-killing medicine to tumor cells.

Other Targeted Therapies:

• Daraxonrasib (Rasonque®): Approved for patients with metastatic PDAC who have received at least one prior systemic treatment or are not candidates for treatment with multiple systemic medicines. It blocks RAS proteins, which help control cell growth and are frequently mutated in pancreatic cancer.
• Erlotinib (Tarceva®): Approved with gemcitabine chemotherapy as first-line treatment for patients with locally advanced pancreatic cancer that cannot be removed by surgery or has spread. It blocks EGFR, a protein involved in cancer cell growth.

Additional targeted therapies may be options for patients with rare tumor mutations, including NTRK or RET gene fusions and BRAF V600E mutations.

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Are There Immunotherapy Clinical Trials for Patients with Pancreatic 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 pancreatic cancer treatment, not only after standard options have stopped working.

Researchers are studying several types of immunotherapy in pancreatic cancer clinical trials, including approaches designed to help more patients respond to treatment, overcome resistance, and improve options for pancreatic cancers that are particularly difficult to treat:

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How Is CRI Advancing Pancreatic Cancer Research?

For decades, the Cancer Research Institute (CRI) has supported scientists working to understand how pancreatic cancer interacts with the immune system and develop more effective immunotherapies. This research spans laboratory discoveries, new treatment strategies, and clinical trials.

CRI-supported research has helped reveal how pancreatic tumors avoid immune attack. Scientific Advisory Council Associate Director Elizabeth Jaffee, MD, and former CRI predoctoral fellow Eric Lutz, PhD, at Johns Hopkins University, demonstrated that an experimental pancreatic vaccine called GVAX could make pancreatic tumors more visible to the immune system. Other CRI-supported studies have explored how KRAS gene mutations can change immune cell behavior and direct immune cells to protect a tumor rather than attack it.

Today, CRI-funded scientists are pursuing several approaches to help more patients benefit from immunotherapy:

• CRI Clinical Innovator Rachael Safyan, MD, at the University of Washington, is leading a clinical trial testing whether adding two immunotherapies to chemotherapy before surgery can break through the barrier that keeps immune cells out of pancreatic tumors. The goal is to shrink tumors, improve surgical outcomes, and reduce the risk of cancer returning.
• CRI Irvington Postdoctoral Fellow Aldo Ummarino, MD, PhD, at Boston Children’s Hospital, is developing a new immunotherapy based on interferons, proteins that help activate immune defenses. Early studies have shown promising results against pancreatic tumors, providing a foundation for future treatment development.
• CRI Dr. Keith Landesman Memorial Fellow Peter Wang, PhD, at Massachusetts General Hospital, is investigating how pancreatic tumors invade nearby nerves and redirect immune cells to protect cancer cells. His research could lead to treatments that protect nerves and strengthen immune responses.
• CRI Irvington Postdoctoral Fellow Anna Kolarzyk, PhD, at Cornell University, is studying how immune cells move between pancreatic tumors and nearby lymph nodes, where immune responses are coordinated. Her work could reveal how these movements change as cancer progresses and identify new opportunities to strengthen immune responses at different stages of disease.