Immunotherapy for Esophageal Cancer
Immunotherapy is the use of medicines that help a person’s own immune system find and destroy cancer cells more effectively. It can be used to treat some people with esophageal (esophagus) cancer.
Immune checkpoint inhibitors
An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.
Drugs called immune checkpoint inhibitors target these checkpoint proteins, which can help restore the immune response against esophageal cancer cells.
PD-1 is a checkpoint protein on immune cells called T cells. When PD-1 attaches to PD-L1, a protein on other cells in the body, it acts as a type of “off switch” that tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack.
Drugs that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.
Examples of PD-1 and PD-L1 inhibitors include:
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo, Opdivo Qvantig)
- Tislelizumab (Tevimbra)
- Durvalumab (Imfinzi)
- Dostarlimab (Jemperli)
These medicines can be used to treat cancers of the esophagus or gastroesophageal junction (GEJ) that can’t be removed with surgery and/or radiation therapy, if the cancer cells test positive for the PD-L1 protein. They might be used with chemotherapy or by themselves if chemotherapy has already been tried.
PD-1 inhibitors might also be used in some other situations. For example:
- Pembrolizumab, dostarlimab, nivolumab (plus ipilimumab; see below), or durvalumab (plus tremelimumab; see below) can be used for some people whose cancer cells have tested positive for specific gene changes, such as a high level of microsatellite instability (MSI-H) or defects in one of the mismatch repair genes (dMMR).
- Pembrolizumab can be used to treat cancers that have a high tumor mutational burden (TMB-H).
- Nivolumab can be used in people who got chemotherapy and radiation (chemoradiation) before surgery, if lab tests after surgery show that some cancer may have been left behind.
- Durvalumab can be used along with chemotherapy before surgery and then by itself after surgery for some earlier stage cancers.
These drugs are typically given once every 2 to 6 weeks, depending on the drug and why it’s being given. All of them can be given as an intravenous (IV) infusion. Nivolumab can also be given as an injection under the skin over several minutes.
CTLA-4 is another checkpoint protein on T cells that normally helps keep them in check.
Ipilimumab (Yervoy) and tremelimumab (Imjudo) are drugs that boost the immune response by blocking the CTLA-4 protein. These drugs are only used along with a PD-1 or PD-L1 inhibitor (see above); they aren’t used by themselves.
These drugs are given as an intravenous (IV) infusion, usually on the same schedule as the PD-1 or PD-L1 inhibitor they’re given with.
Possible side effects of immune checkpoint inhibitors
Common side effects of these drugs can include:
- Fatigue
- Cough
- Nausea
- Poor appetite
- Skin rash or itching
- Constipation or diarrhea
- Muscle or joint pain
- Fever
Other, more serious side effects happen less often. These can include:
Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.
Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.
It’s very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped, and you may get high doses of corticosteroids to suppress your immune system.
More information about immunotherapy
To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
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- References
Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).
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Last Revised: August 14, 2025
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