Immune Checkpoint Therapy: A New Link to Heart Health Concerns
A new study led by researchers at NYU Langone Health and its Perlmutter Cancer Center suggests that a promising cancer therapy may increase patients’ risk of heart attack and stroke. This side effect is potentially caused by immune checkpoint inhibitors’ interference with immune regulation within the heart’s major arteries.
Immune checkpoint inhibitors have revolutionized cancer treatment by unleashing the body’s immune system to attack tumors. These medications work by blocking immune checkpoints, which normally function as “brake pedals” that prevent excessive immune activity and inflammation. Some tumors exploit these checkpoints to evade the immune system, so by blocking them, therapies can empower the immune system to destroy cancerous cells.
However, this treatment approach may unintentionally cause damaging levels of inflammation in the heart, brain, stomach, and other organs. Previous studies have shown that approximately 10% of individuals with atherosclerosis, a condition characterized by hardened fatty deposits (plaques) accumulating within artery walls, experience a heart attack or stroke after undergoing cancer treatment. The precise mechanisms behind this connection have remained unclear until now.
This study delves into the cellular level to explore how immune checkpoint inhibitors interact with immune cells present within arterial plaques. The researchers conducted a genetic analysis that revealed the presence of the same types of immune checkpoints targeted by cancer therapies within these arterial immune cells. This finding establishes a direct link between checkpoint inhibitors and cardiovascular events.
“Our findings offer valuable insights into how a drug intended to target tumors can also trigger an escalated immune response in arteries, subsequently increasing the risk of heart disease,” explains Chiara Giannarelli, MD, PhD, a co-senior author of the study. Giannarelli, an associate professor in the Department of Medicine at NYU Grossman School of Medicine, emphasizes the importance of awareness: “Cancer patients and their physicians should be vigilant and monitor for any new heart concerns following cancer treatment.”
For this study, published online November 29 in the journal _Nature Cardiovascular Research_, the research team examined the genetic activity of thousands of immune cells collected from the plaques of 50 individuals undergoing surgical procedures to address atherosclerosis.
The investigative team further explored the potential role of Type 2 diabetes, a known risk factor for both cancer and heart disease, in exacerbating the ill effects of checkpoint inhibitors in those with atherosclerosis. Giannarelli, also associate professor in the Department of Pathology at NYU Grossman School of Medicine, highlights: “Our results showed that diabetes patients had less measurable communication between checkpoints, which may contribute to increased inflammation.”
Further experiments revealed that taking immune checkpoint inhibitors may hinder the efficacy of conventional treatments for atherosclerosis. Typically, physicians recommend low-fat diets to reduce plaque buildup and inflammation. The researchers’ experiments in rodents confirmed that such diets enhance communication between immune checkpoints within arteries. Cancer patients may be at a disadvantage, however, as their therapy by blocking these checkpoints may counter the anti-inflammatory advantages of a low-fat diet.
“Our findings underscore the interconnectedness of cancer, diabetes, and heart disease—they don’t exist in isolation, and targeting one condition can have ramifications for the others,” states study co-senior author Kathryn Moore, PhD. “Now that experts have a more profound understanding of this interplay, we can explore innovative strategies to minimize the risk of unintended health consequences arising from treatment,” adds Moore, 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.
While the study didn’t directly assess immune checkpoint
What is the potential link between immune checkpoint inhibitors and an increased risk of heart attack and stroke?
## Immune Checkpoint Therapy: A New Link to Heart Health Concerns
**Interviewer:** Welcome back to HealthWatch. Today we’re discussing a really important new study out of NYU Langone Health that sheds light on a potential side effect of a revolutionary cancer treatment: immune checkpoint inhibitors. Joining us is Dr. [Guest Name], a cardiologist specializing in oncology-related heart issues. Dr. [Guest Name], thank you for being here.
**Dr. [Guest Name]:** It’s a pleasure to be here.
**Interviewer:** This study has brought to light a worrying link between these cancer-fighting drugs and an increased risk of heart attack and stroke. Can you explain for our viewers how immune checkpoint inhibitors work and why this unexpected side effect might occur?
**Dr. [Guest Name]:** Absolutely. Immune checkpoint inhibitors are a groundbreaking type of cancer treatment that essentially unleashes the body’s own immune system to fight cancer cells. These drugs work by blocking proteins, called immune checkpoints, that normally act as brakes on the immune system, preventing it from overreacting. Unfortunately, some cancerous cells can exploit these checkpoints to hide from the immune system. [[1](https://www.nature.com/articles/s41586-024-08105-5)]
By blocking these checkpoints, the treatment allows the immune system to recognize and destroy the cancer cells. However, this study suggests that this same mechanism can also trigger an uncontrolled immune response in other parts of the body, including the arteries.
**Interviewer:** So, the immune system, while effectively targeting the cancer, might be inadvertently attacking healthy tissue in the heart?
**Dr. [Guest Name]:** Precisely.
The study found that the same immune checkpoints targeted by these therapies are also present in immune cells within arterial plaques, the fatty deposits that build up inside artery walls. This means that the drug can unintentionally activate these immune cells in the arteries, leading to inflammation and potentially increasing the risk of heart attack or stroke.
**Interviewer:** That’s very concerning. What can be done to mitigate this risk for patients receiving this type of cancer treatment?
**Dr. [Guest Name]:** This is an area of active research. For now, close monitoring is crucial. Patients on immune checkpoint inhibitors should be aware of any potential heart symptoms and report them to their doctor immediately. Regular heart checkups are also important to detect any issues early on.
**Interviewer:** This is certainly a significant development in our understanding of this powerful cancer therapy. Thank you, Dr. [Guest Name], for sharing your expertise on this topic.
**Dr. [Guest Name]:** My pleasure. I hope this information helps raise awareness and encourages open discussions between patients and their doctors.
