New Targets For Triple Negative Breast Cancer Therapies Uncovered

New Targets For Triple Negative Breast Cancer Therapies Uncovered
Credit: Science Photo Library - ROGER HARRIS/Getty Images

A discovery of four new cell types in triple negative breast cancer tumors could lead to new and more effective therapies for patients with this cancer, suggest scientists from the Garvan Institute of Medical Research in Australia.

The research team used RNA sequencing to analyze gene expression in tumors taken from five patients with triple-negative breast cancer. Using this information, they discovered that instead of there only being one type of stromal connective cell in these tumors, as was previously thought, there are actually at least four.

As reported in The EMBO Journal, when the scientists looked into the function of these cell subtypes, they found that one type could suppress immune T cell activity by secreting a protein called CXCL12.

“This is significant because immunotherapy—which is designed to activate the patient’s immune system against a tumor—has limited response in many patients with triple negative breast cancer,” Alex Swarbrick, PhD, an assistant professor at the Garvan Institute and lead author on the study explained.

“If [these cells] 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 the cancer.”

Triple negative breast cancer is so described because it lacks the estrogen, progesterone and HER2 receptors that are often targeted with therapies for other breast cancers. It has a poor prognosis compared with other breast cancers, so new therapy options are desperately needed.

Swarbrick and team sequenced 24,271 individual cells extracted from tumor biopsies from the five breast cancer patients who donated tissue for the study. They found that the stromal cells in the tumor formed four distinct subpopulations.

Two of these groups were cancer-associated fibroblasts – one similar to myofibroblast cells and one with high levels of growth factors and immune regulating molecules such as the T-cell suppressing protein CXCL12. The other two groups were perivascular-like subpopulations of cells, one of these groups contained more differentiated cells and the other more immature cell types.

“Patients with triple negative breast cancers have a poor prognosis, in large part because treatment approaches have advanced very slowly,” said 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.”

Previously stromal cells were only thought to have a structural role in holding the tumor together, so the link between the signaling molecules produced by the stromal cells and immune cells such as T cells is surprising. The researchers think that if this link could be blocked it might help improve the prognosis for patients with this aggressive cancer and plan to investigate this further.

This study forms part of the Breast Cancer Cell Atlas, a project based at the Garvan Institute that plans to sequence a million individual cells from breast cancer tumors to gain more knowledge about the disease and help develop better treatments.