New research has uncovered immune changes in cancer patients that could help identify which patients are most at risk of dangerous heart complications from cancer drugs, known as immune checkpoint inhibitors.

The study was led by Assistant Professor Pilar Martín, head of the Regulatory Molecules of Inflammation Lab at the Spanish National Center for Cardiovascular Research (CNIC) and group leader at CIBER-CV. She explained, “Immune checkpoint inhibitors have revolutionized cancer treatment, but they can also damage the hearts of some patients. In this study we monitored how levels of immune cells, that are known to be involved in the development of heart diseases, change after treatment.”

“We were surprised to see an early and rapid loss of protective immune cells, called regulatory T cells, after cancer patients started treatment. This suggests a window of vulnerability early in treatment,” Assistant Professor Martin continued.

The new research is being presented at European Cardio-Oncology 2025, a scientific congress of the European Society of Cardiology.

Immune checkpoint inhibitors are drugs that work by harnessing the patient’s own immune response to attack cancer cells. Unfortunately, they can also have side effects including causing heart damage, or cardiotoxicity, in some patients. Approximately 1 in 100 patients treated with these drugs develop myocarditis, a life-threatening heart complication.

Researchers found that patients with lower levels of a blood biomarker, called CD69 and found in protective immune cells, experienced a greater decrease in protective immune cells and a resulting increase in destructive pro-inflammatory immune cells. Such a decline in protective immune cells has previously been associated with a greater risk of developing cardiovascular complications such as myocarditis1.

“We put patients into two groups based on their levels of a protective biomarker called CD69, and saw these groups had very different responses to the cancer treatments. Those who had lower levels of CD69 before starting treatment had a more negative immune response which puts them at much greater risk of heart damage.

“More work is needed to validate this biomarker and fully understand the immune changes that are taking place, but testing patients for this biomarker with a blood test is relatively cheap and easy and has the potential to help doctors identify which patients are at greatest risk of complications. This could allow doctors to monitor these patients more closely, and in time I hope we can develop new treatments to prevent the immune dysregulation we see in these patients,” Professor Martin continued.

Researchers analyzed blood samples from 215 cancer patients from the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT) before treatment and at 24 weeks, 10–12 weeks, 6 months, and 1 year after treatment with immune checkpoint inhibitors. The patients had a range of different cancers, including lung, breast and skin cancer, and were treated with different types of immune checkpoint inhibitor treatments, including anti PD1, PDL1 and CTLA4.

Patients were put into two groups dependent on the amount of biomarker for a specific protective T-cell (CD69) in their blood and changes in levels of their immune cell populations were monitored over time.

While both patient groups experienced some decline in levels of a specific type of a protective immune cell (CD69 positive regulatory T cells) in response to treatment, those patients with low starting levels of the protective biomarker had a much larger decrease. These patients also had an increase in immune cells with a role to kill other cells and others that have a role in inflammation.

Regulatory T cells are found in the blood and are important to maintain immune balance and stop the immune system damaging healthy tissues, including the heart and blood vessels. Previous research has shown how the wrong levels of these cells can result in damage to blood vessels and the heart, and this study suggests they could be key in mediating the heart-damaging effects of immune checkpoint inhibitor cancer drugs.