Researchers at Tel Aviv University (TAU) found that immune system cells called neutrophils are recruited by the tumor environment in advanced breast cancer to support tumor progression in the later stages of the disease. They believe that neutrophils, which are unique to the tumor environment, may serve as targets for the development of new drugs and as biomarkers for advanced-stage breast cancer.

The study was led by Dr. Sandra Camargo and PhD student Ori Moskowitz in the laboratory of Dr. Merav Cohen in the Department of Clinical Microbiology and Immunology at TAU’s Gray Faculty of Medical & Health Sciences. The article was published on March 7, 2025, in the journal Nature Cancer.

“In our lab, we study cell-to-cell communication at the single-cell level using an innovative single-cell RNA sequencing method, combined with bioinformatics analyses,” Dr. Cohen explains. “Additionally, we employ a unique method for RNA sequencing of pairs of interacting cells, allowing us to study the communication itself. In the current study, we focused on the intercellular communication between breast cancer cells and neutrophils in the tumor microenvironment.”

Using a mouse model, the researchers collected breast tissue samples at 10 days old and three weeks old (corresponding to breast development in adolescent girls) as well as from healthy adult mice and adult mice with breast cancer. Single-cell RNA sequencing was performed on all samples, and the findings were analyzed using advanced bioinformatics methods. Through this approach, two types of cells were identified as predominantly characterizing advanced-stage cancer tissues: neutrophil immune cells adjacent to cancer cells, and endothelial cells, which among other roles promote blood vessel development.

“From the findings, we inferred that neutrophils play a role in breast cancer,” Dr. Camargo and Ori Moskowitz say. “To explore this further, we examined their molecular communication — that is, the signals they send and receive within their environment. In doing so, we uncovered a complex process that supports tumor growth: cancer cells stimulate macrophages (immune system cells located in the milk ducts of the breast) to recruit neutrophils into the tumor microenvironment. Once there, the neutrophils physically interact with the cancer cells, leading to the secretion of substances that enhance the cancer’s ability to spread and invade additional tissues and increase the formation of blood vessels that nourish the tumor.”

The findings were validated by two additional tests. First, the researchers showed that silencing neutrophils in mice with advanced breast cancer significantly reduced the proliferation of blood vessels and tumor cells. Second, they found that the survival rate of women with late-stage breast cancer (Stages 3 and 4) decreased the more they expressed molecular signatures of neutrophils and their interactions with cancer cells.

“In this study, we uncovered an important mechanism in the development of breast cancer,” Dr. Cohen concludes. “We found that neutrophils play a central role in supporting cancer progression. These findings have dual significance for breast cancer diagnosis and treatment: Neutrophils and the signals they emit may serve both as targets for the development of new drugs and as biomarkers for the advanced stages of the disease.”

Additional contributors included Maiia Levinson, Roy Balaban, Shani Gola, Alice Raizman, and Kelly Lipczyc from Dr. Cohen’s lab; Professor Yaron Carmi, Professor Amir Sonnenblick, Alon Richter, Noa Keren-Khadmy, and Yael Dugach from the Gray Faculty; and researchers from the Weizmann Institute of Science and the Netherlands.