Doxorubicin, a chemotherapy drug used for over 50 years, is highly effective in treating various cancers by slowing down cell division and tumor growth. However, it comes with significant risks, particularly cardiac damage.
This side effect causes the heart to stiffen, potentially leading to heart failure in some patients. Understanding and mitigating these adverse effects remain a challenge, prompting researchers at Tufts University to delve deeper into the drug’s impact on the heart.
Researchers from Tufts University School of Medicine and the Tufts Graduate School of Biomedical Sciences have made a breakthrough in this area. They focused on how doxorubicin affects the immune system, specifically isolating overactive immune cells that contribute to cardiac damage.
Their findings, published in *Nature Cardiovascular Research*, reveal that these immune cells, particularly CD8+ cytotoxic T-cells, play a crucial role in the heart’s inflammatory response to the drug.
The team discovered that doxorubicin increases the levels of these CD8+ T-cells and their attractors in the blood, which then migrate to the heart. This migration causes inflammation and fibrosis in heart tissue, ultimately impairing its function.
The study showed that removing these T-cells could reduce cardiac inflammation and fibrosis, suggesting that targeting these cells might help mitigate the heart damage caused by the drug.
The researchers identified that doxorubicin causes CD8+ T-cells to become dysfunctional, making them recognize heart tissue as foreign and thus overactive. This dysfunction leads these immune cells to attack the heart, though the precise mechanism behind this phenomenon remains unclear.
The study highlights the need for further research to understand why these T-cells are drawn to the heart and to develop strategies to prevent this adverse effect without compromising the drug’s efficacy against cancer.
Future research will explore ways to block the entry of CD8+ T-cells into the heart, potentially leading to safer chemotherapy options. Additionally, the team aims to investigate whether chemokines, the molecules attracting T-cells to the heart, can serve as biomarkers for predicting cardiac damage.
This approach could allow for more personalized and safer treatment regimens. The study also benefits from collaboration with veterinary researchers, applying findings from both human and canine studies to improve treatments for cancer and associated side effects in both species.
