Researchers at the Icahn School of Medicine at Mount Sinai have made an important discovery that could help doctors choose better treatments for patients with recurrent endometrial cancer. Their study, published in the Journal for ImmunoTherapy of Cancer, found specific proteins in the blood (biomarkers) that may predict how well a patient will respond to a combination of two cancer drugs, cabozantinib and nivolumab.

Endometrial cancer (cancer in the lining of the uterus) is the most common gynecologic cancer in the United States, affecting more than 66,000 women each year. The American Cancer Society estimates there will be about 69,120 new cases and about 13,860 deaths from endometrial cancer in the United States in 2025. While immunotherapy is a major treatment option, it does not work for everyone, and many patients experience a return of the disease. This study is the first to examine blood markers that could help doctors personalise treatment and improve patient outcomes.

Scientists identified proteins in the blood that behaved differently in patients receiving nivolumab alone versus those receiving the combination therapy. Patients with lower levels of certain proteins associated with macrophages (a type of white blood cell that plays an integral part in the immune system) before treatment responded better to the drug combination, while some had specific immune activation markers that helped them fight cancer more effectively, leading to longer survival.

Additionally, high levels of proteins related to neutrophils (another type of white blood cell that is an important part of the immune system) were linked to more side effects from the treatment. Notably, the combination therapy worked for some patients who had previously stopped responding to other treatments.

If future research confirms these findings, doctors may be able to use a simple blood test to determine whether a patient is likely to benefit from this treatment. This would help avoid unnecessary treatments and focus on options that offer the best chance of success.

"Our research provides new insights into how the immune system responds to cancer treatment," said lead researcher Sacha Gnjatic, Ph.D., Professor of Immunology and Immunotherapy in the Tisch Cancer Institute of the Icahn School of Medicine at Mount Sinai.

"By identifying specific biomarkers in the blood, we can better predict which patients will benefit from combination therapy, allowing for more personalised and effective treatment strategies. This approach has the potential to improve survival rates while minimising side effects, ultimately advancing the field of cancer immunotherapy."

More information: Vladimir Roudko et al, Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer, Journal for ImmunoTherapy of Cancer (2025). DOI: 10.1136/jitc-2024-010541