scRNA-Seq Analysis Reveals Possible New Targets for Triple-negative Breast Cancer

A team at the Garvan Institute of Medical Research has uncovered four new subtypes of cells within triple-negative cancer—providing promising therapeutic targets for the aggressive disease. Researchers used cellular genomics to identify how one of the newly identified cell types produce molecules that suppress immune cells. Their results were published in EMBO Journal. 

"Patients with triple-negative breast cancers have a poor prognosis, in large part because treatment approaches have advanced very slowly," says senior author Alex Swarbrick. "We've analyzed individual cells in patient tumor samples to gain unprecedented insights into what makes up a tumor, allowing us to identify subtypes of cells and investigate their role in disease."

Because triple-negative breast cancers lack three receptors that are targeted with specialized therapies, it leaves patients with very few options for treatment. The scientists used single-cell RNA sequencing of 24,271 individual cells extracted from biopsy samples of five triple-negative breast cancer patients to detect over 6000 unique RNA molecules in every cell—creating a snapshot of each cell's gene activity.

Their results include that one of the cell subtypes discovered—inflammatory cancer-associated fibroblasts or iCAFs—release the chemokine CXCL12, a signaling molecule known to suppress the anti-tumor activity of T cells. "This is significant because immunotherapy—which is designed to activate the patient's immune system against a tumor—has a limited response in many patients with triple-negative breast cancer," Swarbrick adds. "If iCAFs are suppressing T cells in triple-negative breast cancer, and we can remove this interaction, T cells will be more susceptible to activation and more likely to attack cancer”.

“Cellular genomics is showing us that what we once thought of as one cell type is, in reality, a diversity of cell types, which will have a significant impact on how we tailor treatments in the future," he concludes.