Cutting off blood flow can accelerate tumor growth by prematurely aging the immune system, according to research from NYU Langone Health. The study, published August 19 in JACC: CardioOncology, found that restricted blood flow in the arteries of mice led to breast tumors growing twice as fast compared to those without such restriction.
Peripheral ischemia, which refers to reduced blood flow in the legs due to blocked arteries, was shown to increase cancer progression. This condition is common among people with peripheral artery disease, a problem that affects millions and increases risks for heart attack and stroke.
The researchers noted that this work builds on their earlier findings from 2020, where similar effects were observed following ischemia during a heart attack.
“Our study shows that impaired blood flow drives cancer growth regardless of where it happens in the body,” said Kathryn J. Moore, PhD, corresponding author and Jean and David Blechman Professor of Cardiology at NYU Grossman School of Medicine. “This link between peripheral artery disease and breast cancer growth underscores the critical importance of addressing metabolic and vascular risk factors as part of a comprehensive cancer treatment strategy.”
The study identified that restricted blood flow shifts bone marrow stem cells toward producing more immune-suppressive cells and fewer lymphocytes like T cells, which are essential for fighting cancer. The environment inside tumors also changed in response, accumulating more regulatory T cells and macrophages that protect tumors from immune attack.
Alexandra Newman, PhD, first author and postdoctoral scholar in Dr. Moore’s lab stated: “Our results reveal a direct mechanism by which ischemia drives cancer growth, reprogramming stem cells in ways that resemble aging and promote immune tolerance. These findings open the door to new strategies in cancer prevention and treatment, like earlier cancer screening for patients with peripheral artery disease and using inflammation-modulating therapies, to counter these effects.”
Further experiments indicated these immune changes were long-lasting. Ischemia altered gene expression patterns in immune cells by reorganizing chromatin structure—making it harder for these cells to activate genes needed for attacking tumors.
The research team plans future clinical studies to see if existing inflammation-targeted therapies can help counteract the effects seen after ischemic events.
The study included authors from NYU Langone Health’s Cardiovascular Research Center and Leon H. Charney Division of Cardiology as well as Washington University School of Medicine in Saint Louis. Funding was provided by several American Heart Association grants; National Institutes of Health grants; Sarnoff Cardiovascular Research Foundation; LeDucq Foundation Network; and Laura and Isaac Perlmutter Cancer Center support grant P30CA016087.
