Israeli researchers have discovered that immune system cells called neutrophils are recruited by the tumor environment and support tumor progression in the later stages of the disease.
“In light of our findings, we 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 researchers said.
The study was conducted at Tel Aviv University’s Gray Faculty of Medical & Health Sciences using advanced technologies to focus on the tumor microenvironment in advanced stages of breast cancer.
Dr. Sandra Camargo and PhD student Ori Moskowitz led the research in the laboratory of Dr. Merav Cohen in the Department of Clinical Microbiology and Immunology at the Gray Faculty of Medical & Health Sciences at Tel Aviv University, along with researchers from the Weizmann Institute of Science and the Netherlands.
The findings were published in the prestigious 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,” Cohen said. “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 four different stages: at 10 days old, 3 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, Camargo and Moskowitz said. “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. We found that neutrophils — immune system cells recruited into the tumor environment — 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,” Cohen added.
