How Restricted Blood Flow Accelerates Tumor Growth by Accelerating Immune Aging

Recent research from NYU Langone Health reveals that limited blood flow, particularly in the arteries of the legs, can significantly influence tumor development. The study demonstrates that ischemia—caused by the buildup of fatty deposits such as cholesterol—creates a hostile environment by promoting immune system aging and suppressing the body’s ability to combat cancer. When blood flow is obstructed, it causes premature aging of the bone marrow, the source of critical immune cells, leading to a shift in the immune cell population. This shift favors cells that dampen immune responses, making it easier for tumors to grow and evade detection.

Published in JACC-CardioOncology, the study showed that mice with restricted blood flow in their legs experienced breast tumors growing at twice the rate compared to mice with normal blood flow. These findings extend previous work by the same team, which found that ischemia during heart attacks accelerates similar immune aging processes.

The research involved creating a mouse model with induced limb ischemia to observe its effects on tumor growth and immune cell populations. The team explained that in response to reduced blood flow, stem cells in the bone marrow are reprogrammed, leading to an increase in myeloid immune cells like monocytes, macrophages, and neutrophils that suppress immune responses. Meanwhile, cells responsible for mount anti-tumor activity, such as T lymphocytes, are decreased.

Additionally, within the tumor environment, there was an accumulation of immune-suppressive cells, including Ly6Chi monocytes, M2-like macrophages, and regulatory T cells that protect tumors from immune attack. These immune alterations are not fleeting; ischemia causes long-lasting changes, including modifications in gene expression and chromatin restructuring, which further inhibit immune cells' ability to fight cancer.

According to lead researcher Dr. Kathryn J. Moore, this study highlights the vital link between vascular health and cancer progression, emphasizing the need to address vascular and metabolic risks as part of comprehensive cancer management. The findings suggest that inflammation-modulating therapies and early screening for patients with peripheral artery disease could be promising strategies for mitigating tumor growth driven by ischemic conditions.

Looking ahead, the team plans to investigate whether existing anti-inflammatory treatments can offset post-ischemic changes that promote tumor growth, aiming to improve cancer prevention and therapy outcomes.