Cancer Treatment Breakthrough: Reducing Heart Risks with New Insights into Immunotherapy
For many cancer patients, immune checkpoint inhibitors (ICIs) like Keytruda and Opdivo have been life-changing. However, a potentially fatal side effect – inflammation of the heart tissue, known as myocarditis – has limited their apply. Now, researchers at Cincinnati Children’s Hospital have made a significant discovery that could dramatically improve the safety of these powerful treatments.
The Promise of Immune Checkpoint Inhibitors
ICIs work by unleashing the body’s own immune system to fight cancer. They achieve this by blocking “checkpoint” proteins that cancer cells use to evade detection by T cells. Since the first ICI, Yervoy, was approved in 2011 for melanoma treatment, these therapies have revolutionized outcomes for numerous cancer types, earning James Allison and Tasuku Honjo the 2018 Nobel Prize in Medicine.
A Deadly Trade-off: Myocarditis and ICIs
Despite their success, ICIs carry a risk of myocarditis, affecting approximately 2% of patients. Tragically, about half of those who develop this inflammation do not survive, even if their cancer responds to treatment. This serious complication has created a critical need for strategies to mitigate the risk.
Unraveling the Mechanism: TNF and Autoreactive T Cells
The research team at Cincinnati Children’s developed a new mouse model to accurately replicate ICI-induced myocarditis. Through advanced experiments, they identified CD8 T cell-derived tumor necrosis factor (TNF) as a key driver of the condition.
Crucially, the study revealed that this heart inflammation isn’t caused by the immune system exhausting cancer-specific T cells. Instead, ICIs can trigger the production of “autoreactive” T cells that mistakenly attack healthy heart muscle cells alongside cancer cells.
Blocking TNF: A Potential Solution
The researchers demonstrated that blocking TNF signaling, specifically through the TNFR2 gene product, prevented the inflammatory cycle in the hearts of mice. This suggests that targeting TNF could prevent cardiac toxicity without compromising the anti-tumor benefits of ICIs.
“Checkpoint inhibitors allow TNF signaling to trigger CD8 T-cells that are specific to antigens on cardiac myocytes, which in turn leads to life-threatening arrythmias,” explained Jeffery Molkentin, PhD, director of the Division of Molecular Cardiovascular Biology at Cincinnati Children’s.
What’s Next for ICI Safety?
Although these findings are promising, further research is essential. Scientists need to determine the safety of narrowly focused TNF inhibitors for human use and the optimal duration of treatment. TNFR2-specific antibodies are currently in development.
The team too aims to investigate whether similar approaches can prevent immune-related adverse events affecting other organs. This could pave the way for broader applications of immunotherapy with reduced side effects.
Did you know?
The Nobel Prize in Medicine was awarded in 2018 to James Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.
Frequently Asked Questions
- What are immune checkpoint inhibitors? ICIs are a type of cancer treatment that helps the immune system recognize and destroy cancer cells.
- What is myocarditis? Myocarditis is inflammation of the heart muscle, which can be a life-threatening side effect of some cancer treatments.
- What is TNF? Tumor necrosis factor (TNF) is a signaling molecule identified as a key driver of heart inflammation in patients receiving ICIs.
- Is this research applicable to all cancer patients? More research is needed to determine the broad applicability of these findings, but the initial results are promising.
Stay informed about the latest advancements in cancer treatment. Explore more articles on immunotherapy and related topics to learn how these breakthroughs are shaping the future of cancer care.
