Immune checkpoint inhibitors, a key class of cancer therapies, may heighten cardiovascular risk by triggering damaging levels of inflammation in the heart, new research suggests.
Summary: A new study from NYU Langone Health highlights how immune checkpoint inhibitors, a widely used cancer treatment, may increase the risk of heart attack and stroke by disrupting immune regulation in arterial plaques. These drugs block molecules that normally prevent excess immune activity, allowing the immune system to attack tumors. However, this mechanism may also induce harmful inflammation in the heart and other organs. The study also examined how type 2 diabetes amplifies the cardiovascular risks associated with these treatments, revealing that diabetes patients may experience diminished immune checkpoint communication, further increasing inflammation.
Key Takeaways:
- Cancer Treatment and Cardiovascular Risk: Immune checkpoint inhibitors, while effective against tumors, can disrupt immune regulation in arteries, increasing the risk of heart attack and stroke.
- Impact of Diabetes: Type 2 diabetes may exacerbate the cardiovascular risks of immune checkpoint inhibitors by impairing immune checkpoint communication, leading to heightened inflammation.
- Interplay of Conditions: The study underscores the interconnected nature of cancer, diabetes, and heart disease, highlighting the need for tailored strategies to mitigate unintended cardiovascular side effects of cancer therapies.
A cancer therapy that prompts the body’s immune defenses against viruses and bacteria to attack tumors can make patients more vulnerable to heart attack and stroke. A possible explanation for this side effect is that the treatment interferes with immune regulation in the heart’s largest blood vessels, a new study suggests.
Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the new work focused on a potent class of cancer-fighting drugs called immune checkpoint inhibitors. These medications work by blocking molecules embedded on the surface of cells—immune checkpoints—which normally serve as “brake pedals” that prevent excess immune activity, or inflammation.
Some tumors are known to hijack these checkpoints to weaken the body’s defenses, so by blocking the checkpoints, the treatments enable the immune system to kill tumor cells.
However, this treatment type may also trigger damaging levels of inflammation in the heart, brain, stomach, and other organs, the researchers say. For example, past studies have shown that about 10% of those with atherosclerosis have a heart attack or stroke following cancer treatment. However, the specific mechanisms behind this issue had until now remained unclear.
Immune Checkpoint Inhibitors and Cardiovascular Risks
To address this question, the research team explored at a cellular level how immune checkpoint inhibitors interact with immune cells within arterial plaques. A genetic analysis by the study authors showed that the same type of immune checkpoints targeted by cancer therapies also appear in arterial immune cells, establishing a link between checkpoint inhibitors and cardiovascular events.
“Our findings provide new insight into how a drug intended to target tumors can also prompt a heightened immune response in arteries and increase risk of heart disease,” says study co-senior author Chiara Giannarelli, MD, PhD, an associate professor in the Department of Medicine at NYU Grossman School of Medicine, in a release. “Cancer patients and their physicians should be aware that they may need to monitor for new heart concerns following cancer treatment.”
For the current study, which was published in Nature Cardiovascular Research, the researchers analyzed the genetic activity of thousands of immune cells collected from the plaques of 50 men and women undergoing a surgical procedure to address atherosclerosis.
Diabetes and Atherosclerosis: A Compounding Risk
The investigators also explored how type 2 diabetes, a known risk factor for both cancer and heart disease, may make those with atherosclerosis even more vulnerable to the ill effects of checkpoint inhibitors, adds Giannarelli, also associate professor in the Department of Pathology at NYU Grossman School of Medicine.
As part of the study, the team assessed immune checkpoint activity in arterial tissue collected from eight patients with diabetes and four healthy volunteers. Notably, none had a history of atherosclerosis. The results showed that the diabetes patients had less measurable communication between checkpoints, which in turn can prompt increased inflammation.
Other experiments further revealed that taking immune checkpoint inhibitors might make it harder to combat atherosclerosis. Under normal circumstances, physicians typically prescribe low-fat diets to reduce plaque buildup and inflammation. Indeed, the researchers’ experiments in rodents confirmed that such diets boost communication between immune checkpoints within arteries. However, cancer patients may be at a disadvantage because their therapy, by blocking these same checkpoints, may counteract the anti-inflammatory benefits of fat reduction.
A Call for Comprehensive Care
“Our findings highlight how cancer, diabetes, and heart disease do not exist in a vacuum and that it is critical to consider how targeting one of these conditions can affect the others,” says study co-senior author Kathryn Moore, PhD, the Jean and David Blechman Professor of Cardiology at NYU Grossman School of Medicine, where she also serves as director of its Cardiovascular Research Center, in a release. “Now that experts have a better understanding of the interplay between these diseases, they can begin to explore new strategies to lower the risk of unintended health concerns caused by their treatment.”
Moore, also a professor in the Department of Cell Biology at NYU Grossman School of Medicine, cautions that the study did not directly assess immune checkpoint behavior in cancer patients. The team plans to do so in future investigations, she adds.
