Innovative Approach Uses Neutrophil Reprogramming to Combat Breast Cancer

A groundbreaking study by researchers from McGill University, the Lady Davis Institute for Medical Research at the Jewish General Hospital, Princess Margaret Cancer Center, and MIT unveils a novel strategy to fight aggressive breast cancers. The research focuses on retraining neutrophils, the body's first responders, to directly attack tumor cells, offering new hope for patients with breast cancers resistant to existing immunotherapies.

Traditional immunotherapy mainly targets T cells to stimulate an immune response against tumors. However, many breast cancers, especially the immune cold types, lack sufficient T cell infiltration, reducing the effectiveness of such treatments. The new approach, detailed in Science Advances, shifts focus toward harnessing the innate immune system by educating neutrophils to develop tumoricidal properties.

The study demonstrates that combining systemic Toll-like receptor (TLR) agonists with mitochondrial complex I inhibitors boosts neutrophil activity. This combination prompts neutrophils to produce reactive oxygen species (ROS) and cytotoxic granules, enabling them to kill breast cancer cells independently of T cell-mediated immunity. This mechanism is particularly promising for overcoming resistance in forms like triple-negative breast cancer, which currently has limited treatment options.

According to lead researcher John Heath, the strategy exploits innate immunity, transforming neutrophils into potent anti-cancer agents. Josie Ursini-Siegel highlights that neutrophils can be reprogrammed to effectively target tumors that evade traditional immune responses. Importantly, experiments confirmed that removing neutrophils nullifies the anti-tumor effects, underscoring their essential role.

This dual approach enhances neutrophil recruitment to tumor sites and amplifies their cytotoxic functions. By increasing NADPH oxidase activity and NF-κB signaling, the treatment induces oxidative damage in cancer cells. Furthermore, the study underscores the importance of understanding tumor-immune interactions to develop therapies that activate immune surveillance mechanisms rather than fostering a pro-tumorigenic microenvironment.

Overall, this research paves the way for innovative treatments targeting the innate immune system, broadening the horizon for managing resistant breast cancers and potentially revolutionizing immunotherapy strategies.

Source: https://medicalxpress.com/news/2025-07-reveals-strategy-retrain-neutrophils-breast.html