Reduced blood flow can prematurely age bone marrow, which weakens the immune system's capacity to combat cancer, according to a new study from NYU Langone Health.
Published in JACC-CardioOncology, the study demonstrates that peripheral ischemia—restricted blood flow in leg arteries—led breast tumors in mice to grow at double the rate compared to those with unrestricted flow. This complements a 2020 finding by the same team linking ischemia during heart attacks to similar effects.
JACC-CardioOncologyIschemia occurs when fatty deposits like cholesterol build up in artery walls, causing inflammation and clots that restrict oxygen-rich blood flow. When affecting the legs, this condition leads to peripheral artery disease, impacting millions of Americans and heightening heart attack or stroke risks.
"Our research demonstrates that impaired blood flow promotes cancer growth regardless of its location in the body," says Dr. Kathryn J. Moore, Ph.D., Jean and David Blechman Professor of Cardiology at NYU Grossman School of Medicine.
"This connection between peripheral artery disease and breast cancer emphasizes the importance of addressing metabolic and vascular risk factors in comprehensive cancer treatment strategies."
Notably, the research team discovered that restricted blood flow shifts immune cell populations toward those less effective against infections and cancer, mirroring age-related changes.
To investigate the link between cardiovascular disease and tumor growth, researchers developed a mouse model with breast tumors, inducing temporary ischemia in one hind limb. They then compared cancer progression in mice with and without impaired blood flow.
The study builds on the immune system's evolutionary role: it attacks bacteria and viruses and eliminates cancer cells under normal conditions using stem cell reserves in bone marrow for producing key white blood cell populations throughout life.
Typically, the immune system heightens inflammation to combat threats but scales back to avoid harm to healthy tissue. This balance is maintained by a mix of immune cells that either activate or suppress inflammation.
The researchers found reduced blood flow disrupts this equilibrium. It reprograms bone marrow stem cells to favor the production of "myeloid" immune cells (monocytes, macrophages, neutrophils) that dampen immune responses, while decreasing output of active lymphocytes like T cells essential for strong anti-tumor responses.
Tumors showed a similar shift with more immune-suppressive cells—including Ly6Chi monocytes, M2-like F4/80+ MHCIIlo macrophages, and regulatory T cells—that shield cancer from the immune system.
The changes were found to be long-lasting. Ischemia altered expression of hundreds of genes, forcing immune cells into a more cancer-tolerant state, while reorganizing chromatin structure—the protein framework controlling DNA access—making it difficult for immune cells to activate cancer-fighting genes.
"Our results unveil a direct mechanism by which ischemia accelerates cancer growth, reprogramming stem cells in ways that resemble aging and promote immune tolerance," says first author Alexandra Newman, Ph.D., a postdoctoral scholar in Dr. Moore’s lab.
"These findings suggest new strategies for cancer prevention and treatment, such as early screening for patients with peripheral artery disease and using inflammation-modulating therapies to counteract these effects."
The research team aims to design clinical studies evaluating whether existing inflammation-targeted therapies can reverse post-ischemic changes driving tumor growth.