Immunotherapy and the Heart: Low CD69 Levels May Increase the Risk of Cardiac Damage!

In recent years, immune checkpoint inhibitors , a class of immunotherapies, have brought about a revolution in cancer treatment.

In many cancers, including lung cancer, melanoma, kidney cancer, and breast cancer, these treatments can significantly prolong survival. Yet one issue remains overshadowed by these success stories and has not received enough attention: their potential harmful effects on heart health.

📍 At the European Society of Cardiology's Cardio-Oncology Conference in Florence on 20 June 2025, findings from the SIR-CVT studywere presented, showing that low levels of CD69 , an immune-cell receptor, may significantly increase the risk of cardiac damage after immunotherapy .

The most serious cardiac adverse effects of immunotherapy include:

• Myocarditis (inflammation of the heart muscle) – one of the most serious adverse effects
• Pericarditis, arrhythmia, conduction abnormalities
• Cardiomyopathy (weakness of the heart muscle)

📊 A study involving more than 2600 patients receiving ICIs reported a 1% rate of immunotherapy-induced myocarditis . In addition, elevations in biomarkers such as CPK, troponin T, ALT, and AST may provide early signals of these toxicities.

• Number of participants: 215 patients in the initial phase (target 500)
• 57% of participants: Non-small cell lung cancer
• Median age: 68
• 83%: Had at least one cardiovascular risk factor
• Patients with low CD69 levels: Had a risk of heart disease that was 2 times higher .

📆 Blood samples were collected at the following times:

• Before treatment
• 2–4 weeks
• 10–12 weeks
• 6 months
• 1 year

• Within the first 3 weeks: A marked decline in CD69+ regulatory T cells
• This decline: Was sharper in patients with low CD69 levels
• Result: Loss of peripheral immune tolerance → cardiac inflammation
• Additional findings:
  • Increase in Th17 cells → proinflammatory response
  • Increase in CD8+ cytotoxic cells → direct damage to heart tissue

This study offers an important opportunity to identify patients at risk of cardiotoxicity in advance .

• An individualized risk profile could be developed based on CD69 levels
• During immunotherapy, closer cardiac monitoring
• Early intervention to prevent serious complications
• Reducing unnecessary treatment interruptions

• Routine assessment of CD69 levels
• Early diagnosis using new biomarkers such as miR-721
• Strengthening interdisciplinary oncology-cardiology collaboration
• Developing personalized cardio-oncology monitoring strategies

Immunotherapy is extending the lives of many cancer patients. However, ignoring these treatments' effects on heart healthcan sometimes have irreversible consequences.

CD69 levelsmay be more than a biomarker: if assessed in time, they could provide an early-warning system that saves lives .