For many people living with advanced or recurrent uterine (endometrial) cancer, immunotherapy has opened the door to new treatment possibilities. While chemotherapy has long been a standard treatment option, immunotherapy works in a very different way by helping the body’s own immune system recognize and attack cancer cells.
According to UCSF Health’s Dr. Katherine Fuh, immunotherapy has become an especially important area of research and treatment in uterine (endometrial) cancer, particularly for patients whose cancer has returned or spread.
What is immunotherapy?
Immunotherapy is a broad term used to describe treatments that help the immune system fight cancer. In uterine (endometrial) cancer, doctors commonly use a type of immunotherapy called PD-1 or PD-L1 inhibitors.
Dr. Fuh explains that PD-1 is a protein found on immune cells called T cells, while PD-L1 is found on tumor cells. Cancer cells can use this interaction to “hide” from the immune system.
“The tumor cells are very clever,” Dr. Fuh says. She describes the interaction between PD-1 and PD-L1 “like a dance” where the immune cells and cancer cells recognize each other and essentially become “friends,” preventing the immune system from attacking the cancer.
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Immunotherapy interrupts that process. “When we do deliver anti-PD1, it takes away that PD-1 on the immune cells,” Dr. Fuh shares. Without that signal, “the immune cell then attacks that tumor cell.”
How is immunotherapy different from chemotherapy?
Although immunotherapy and chemotherapy are both cancer treatments, they work in very different ways.
Chemotherapy directly attacks rapidly dividing cells, including cancer cells. Dr. Fuh explains that chemotherapy “targets the tumor cells themselves.” Immunotherapy activates the immune system to do the work.
That distinction is important because it also means the side effects can differ significantly between the two treatments.
Who is a right fit for immunotherapy?
Dr. Fuh highlights that immunotherapy is most commonly used for patients with advanced or recurrent uterine (endometrial) cancer. It may be given alone or in combination with chemotherapy depending on the specific characteristics of the tumor.
Biomarker testing also plays a major role in determining who may benefit most from immunotherapy. In particular, tumors that are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) often respond especially well to these treatments.
Researchers are continuing to study whether immunotherapy could also help patients with earlier-stage disease who may still have a high risk of recurrence.
“It is under study,” Dr. Fuh says. Clinical trials are currently exploring whether patients with high-risk early-stage tumors — especially those that are mismatch repair deficient — may benefit from combining radiation and immunotherapy.
Some studies have already looked at adding immunotherapy earlier in treatment, though results have varied. Dr. Fuh notes that researchers are still waiting for more data to better understand which patients benefit most in these settings.
Possible side effects of immunotherapy
Side effects can sometimes occur when the immune system mistakenly attacks healthy organs and tissues. One side effect shared by both chemotherapy and immunotherapy is fatigue. However, immunotherapy also has its own unique set of possible immune-related side effects.
Dr. Fuh says thyroid problems are among the more common side effects seen in uterine (endometrial) cancer patients receiving immunotherapy. “We do check the thyroid-stimulating hormones and thyroid tests to really keep an eye on that,” she explains.
Other possible side effects include:
- Pneumonitis: inflammation of the lungs that may cause shortness of breath, fever, or worsening fatigue
- Hepatitis: inflammation of the liver, monitored through liver function blood tests
- Colitis: inflammation of the colon that can lead to severe diarrhea
Dr. Fuh emphasizes that patients should report symptoms promptly, especially breathing changes or significant diarrhea, because some immune-related side effects can become serious if not treated early.
Why clinical trials matter
Immunotherapy continues to evolve rapidly in uterine cancer care. Ongoing clinical trials are helping researchers better understand:
- Which patients benefit most from immunotherapy
- Whether immunotherapy should be used earlier in treatment
- How immunotherapy works alongside radiation or chemotherapy
- Which biomarkers can best predict response
For patients interested in newer treatment approaches, asking about clinical trials may be an important part of the conversation with their care team.
As research continues, doctors hope to better identify which patients are most likely to benefit and whether immunotherapy may eventually play a larger role in earlier-stage uterine cancer treatment.
Hear more from Dr. Fuh and watch the full webinar discussion here.
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