Long distance signalling and breast cancer metastatic spread: a neutrophil story

A recent study from Hannah Garner, Ph.D. and new member of the Rosalind and Morris Goodman Cancer Institute (GCI), published in Cancer Cell, showed that neutrophil precursors located in the bone marrow receive signals from mammary tumours and promote metastasis.

Neutrophils are immune cells that arise in the bone marrow and respond to signals from all over the body. In the context of breast cancer, it is known that primary tumours drive the systemic accumulation and polarization of neutrophils which promote metastatic spread. However, it remained unknown where and how neutrophils become educated by a distant mammary tumour.

To answer this question, Dr. Garner and her colleagues used a variety of techniques to demonstrate that neutrophil progenitors are educated to become pro-tumorigenic early in neutrophil development, receiving signals from the mammary tumours when they are still in the bone marrow. They went even further and showed that interleukin-1b  (IL-1b), a pro-inflammatory cytokine, promotes this activation of neutrophils. They treated mammary tumour-bearing mice with anti-IL-1b antibodies, which significantly reduced lymph node and lung metastases compared to the control group.

These promising findings suggest that using IL-1b inhibitors, which are already used to treat other inflammatory diseases such as arthritis, could be used in the future to reduce breast cancer metastatic spread. Further studies are needed to bring this to the clinic. This collaborative research, co-led by Hannah Garner, Ph.D., Moreno Martinovic, Karin E. de Visser, Ph.D., and Elzo de Wit, Ph.D., paves the way for better cancer outcomes for patients and is a step forward in our quest to find the #knowledgetocure.

To learn more, read the publication “Understanding and reversing mammary tumour-driven reprogramming of myelopoiesis to reduce metastatic spread”