New techniques are allowing experts to examine the broad cancer ‘ecosystem’ that supports a tumour to grow and spread.

Using advanced cellular genomics, researchers from the Garvan Institute of Medical Research have uncovered four new subtypes of cells within triple negative breast cancer, which contain promising new therapeutic targets for the aggressive disease.

One of the new cell types produces molecules that suppress immune cells, and may help cancer cells evade the body’s immune system.

The experts say their new technique could lead to a new class of therapies for triple negative breast cancer.

“Patients with triple negative breast cancers have a poor prognosis, in large part because treatment approaches have advanced very slowly,” says senior author Associate Professor Alex Swarbrick, Head of the Tumour Progression Laboratory at Garvan.

“We’ve analysed individual cells in patient tumour samples to gain unprecedented insights into what makes up a tumour, allowing us to identify subtypes of cells and investigate their role in disease.”

Triple negative breast cancers lack three receptors (for oestrogen, progesterone and the HER2 protein) that are targeted with specialised therapies in other breast cancers.

This leaves patients with limited treatment options and poor outcomes – a substantial proportion of patients diagnosed with the cancer die within five years of diagnosis.

The new study looked for new potential targets for therapy by analysing the individual cells inside triple negative breast tumours - not only the cancer cells themselves, but also the surrounding host cells, such as immune and connective tissue cells.

This can be thought of as the cancer ‘ecosystem’ that supports a tumour to grow and spread.

The researchers used next-generation sequencing of 24,271 individual cells extracted from biopsy samples of five triple negative breast cancer patients, and detected over 6,000 unique RNA molecules in every cell, creating a snapshot of each cell’s gene activity.

By analysing the profiles of active genes, the researchers revealed four cell subtypes of stromal cells, which form the connective tissues in the body. Previous studies in triple negative breast cancers had generally considered there to be only one type of stromal cell.

Further investigations found surprising interactions between the signalling molecules produced by the stromal cells and immune cells.

“Our findings suggest that there is significant crosstalk between the immune system and stromal cells, which were generally thought to have only a structural role in cancers,” says Associate Professor Swarbrick.

The researchers say that combining immunotherapy with a treatment that stops the interaction between stromal cells and immune cells holds promise for improving the treatment of triple negative breast cancer.

The study is accessible here.