Neutrophil immune cells may serve as a target for new therapies and a biomarker for advanced-stage breast cancer

Researchers at the Faculty of Medical and Health Sciences at Tel Aviv University conducted a series of experiments using advanced technologies, focusing on the tumor microenvironment in advanced stages of breast cancer. They found that immune cells called neutrophils are recruited by the tumor environment and support cancer progression at advanced stages of the disease. The researchers stated: "Based on our findings, we believe that neutrophils, which are unique to the tumor microenvironment, may serve as a target for the development of new therapies, as well as a biomarker for advanced-stage breast cancer."

From right: researchers Uri Moskowitz, Dr. Merav Cohen, and Maya Levinson from the Department of Microbiology and Clinical Immunology

The study was led by Dr. Sandra Camargo and PhD candidate Uri Moskowitz in the laboratory of Dr. Merav Cohen, at the Department of Microbiology and Clinical Immunology, Faculty of Medicine and Health Sciences, Tel Aviv University. Additional contributors to the study included Maya Levinson, Roy Balevan, Shani Gola, Alice Reisman, and Kelly Lifshitz from Dr. Cohen’s lab; Prof. Yaron Carmi, Prof. Amir Sonnenblick, Alon Richter, Noa Keren-Kedmi, and Yael Dogatch from the Faculty of Medicine and Health Sciences at Tel Aviv University; as well as researchers from the Weizmann Institute of Science and from the Netherlands. The paper was published in the prestigious journal Nature Cancer.

Dr. Cohen explains:
"In our lab, we study cell-to-cell communication at the single-cell level, applying an innovative method of single-cell RNA sequencing, combined with bioinformatics analyses. In addition, we use a unique method for RNA sequencing of physically interacting cell pairs, which allows us to investigate the communication itself. In the current study, we focused on the interaction between breast cancer cells and neutrophils within the tumor microenvironment."

The researchers used a mouse model and collected mammary tissue samples at four different stages: at 10 days old, at 3 weeks old—corresponding to early breast development in adolescent girls—as well as from healthy adult mice and adult mice with breast cancer. RNA sequencing at the single-cell level was performed on all samples, and the findings were analyzed using advanced bioinformatics methods. Through this approach, two types of cells were identified as being particularly associated with advanced-stage cancer tissues: immune system neutrophils physically adjacent to tumor cells, and endothelial cells, which among other roles, support blood vessel development.

Dr. Camargo and Uri Moskowitz state:
"From the findings, we inferred that neutrophils play a role in breast cancer. To explore this in depth, we examined their molecular communication—meaning the signals they send and receive from surrounding cells. This allowed us to uncover a complex process that supports tumor growth: breast cancer cells prompt macrophages (immune cells located in the mammary ducts) to recruit neutrophils to the tumor environment. Once there, neutrophils physically interact with the cancer cells, leading to the secretion of factors that enhance the cancer’s ability to spread and invade other tissues, as well as promote the formation of new blood vessels that nourish the tumor."

The findings were validated by two additional experiments:
First, the researchers showed that silencing neutrophils in mice with advanced-stage breast cancer significantly reduced tumor cell proliferation and blood vessel formation.
Second, analysis revealed that in women with advanced-stage breast cancer (stages 3 and 4), higher expression of neutrophil molecular signatures—and of the interaction between neutrophils and tumor cells—was associated with lower survival rates.

Dr. Cohen concludes:
"In this study, we uncovered an important mechanism in breast cancer development. We found that neutrophils—immune cells recruited to the tumor environment—play a key role in supporting cancer progression. These findings have dual significance for breast cancer diagnosis and therapy: neutrophils, and the signals they produce, may serve as targets for new drug development, as well as biomarkers for advanced-stage disease."

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