A cancer treatment that encourages the body’s immune system to attack tumors, similar to how it fights viruses and bacteria, might increase the risk of patients experiencing heart attacks and strokes. A new study offers a possible explanation for this side effect, indicating that the therapy may disrupt immune regulation in the large blood vessels of the heart.
A cancer treatment that encourages the body’s immune system to attack tumors, similar to how it fights viruses and bacteria, might increase the risk of patients experiencing heart attacks and strokes. A new study offers a possible explanation for this side effect, indicating that the therapy may disrupt immune regulation in the large blood vessels of the heart.
Researchers from NYU Langone Health and its Perlmutter Cancer Center led the study, which focused on a strong category of cancer treatments known as immune checkpoint inhibitors. These drugs function by blocking specific molecules at the cell surface, known as immune checkpoints, which typically act as “brakes” to prevent excessive immune responses or inflammation. Some tumors exploit these checkpoints to diminish the body’s defense against cancer. By blocking these checkpoints, the treatments empower the immune system to eliminate tumor cells.
However, this type of treatment might also provoke harmful inflammation in the heart, brain, stomach, and other organs, according to the researchers. Previous studies indicated that about 10% of individuals with atherosclerosis—a condition marked by the buildup of hardened fatty deposits, or plaques, in the arteries—experience heart attacks or strokes following cancer treatments. Yet, the specific mechanisms responsible for this issue had not been clearly understood until now.
To investigate this, the research team examined how immune checkpoint inhibitors interact with immune cells within arterial plaques at a cellular level. A genetic analysis revealed that the same immune checkpoints targeted by cancer therapies are present in the immune cells of arteries, suggesting a connection between checkpoint inhibitors and cardiovascular incidents.
“Our findings offer new insights into how a medication designed to combat tumors can also lead to an enhanced immune response in arteries, thereby increasing the risk of heart disease,” stated Chiara Giannarelli, MD, PhD, a co-senior author of the study. “Cancer patients and their healthcare providers should be mindful of potential new heart issues following cancer treatment,” she added. Giannarelli is also an associate professor in the Department of Medicine at NYU Grossman School of Medicine.
The current study, published online on November 29 in the journal Nature Cardiovascular Research, involved analyzing the genetic activity of thousands of immune cells collected from the plaques of 50 patients undergoing surgery for atherosclerosis.
The researchers also examined the impact of Type 2 diabetes—a known risk factor for cancer and heart disease—on patients with atherosclerosis and their susceptibility to the negative effects of checkpoint inhibitors. The team assessed immune checkpoint activity in arterial tissues taken from eight patients with diabetes and four healthy individuals, noting that none of the participants had a history of atherosclerosis. The results indicated that patients with diabetes exhibited less effective communication among immune checkpoints, which could lead to increased inflammation.
Additional experiments showed that using immune checkpoint inhibitors may hinder efforts to fight atherosclerosis. Normally, doctors recommend low-fat diets to reduce plaque accumulation and inflammation. Indeed, experiments conducted on rodents verified that such diets enhance communication among immune checkpoints within arteries. However, cancer patients may face challenges because their treatment—which blocks these same checkpoints—could negate the anti-inflammatory effects associated with fat reduction.
“Our findings underscore the interconnectedness of cancer, diabetes, and heart disease, highlighting the importance of considering how targeting one condition can influence the others,” remarked study co-senior author Kathryn Moore, PhD. “With a better understanding of how these diseases interact, experts can start to develop new strategies to minimize the risk of unintended health issues arising from treatment,” added Moore, who is the Jean and David Blechman Professor of Cardiology at NYU Grossman School of Medicine and director of its Cardiovascular Research Center.
Moore, also a professor in the Department of Cell Biology at NYU Grossman School of Medicine, points out that this study did not directly evaluate immune checkpoint activity in cancer patients. The team intends to investigate this in the future, she notes.
The study received funding from several National Institutes of Health grants and other organizations, including the American Heart Association and the Chan Zuckerberg Institute.
Besides Moore and Giannarelli, José Gabriel Barcia Durán, PhD, and Michael Gildea, PhD, contributed as co-lead authors. Other NYU Langone researchers included Letizia Amadori, PhD; Morgane Gourvest, PhD; Ravneet Kaur, MS; Natalia Eberhardt, PhD; Panagiotis Smyrnis, MD, PhD; Burak Cilhoroz, PhD; Swathy Sajja, MS; Navneet Narula, MD; Rami Vanguri, PhD; Ira Goldberg, MD; Edward Fisher, MD, PhD; and Jeffrey Berger, MD. Additional contributors from the Icahn School of Medicine at Mount Sinai include Karishma Rahman, MD, PhD; Dawn Fernandez, PhD; and Peter Faries, MD.
