Understanding how triple negative breast cancer hides from the immune system

Triple negative breast cancer can be more aggressive than other types of breast cancer. It's also more likely to come back in the first few years after treatment, and more likely to spread to other organs. When it spreads, we call this secondary breast cancer. Secondary breast cancer can be treated, but it’s currently incurable.

We need to understand how triple negative breast cancer can resist current treatments – and use this knowledge to find more effective ways to treat it.

Breast tumours aren’t made up of only breast cancer cells. There are many different types of immune and healthy cells in a tumour. We call this the tumour microenvironment, and it changes as the tumour grows.

The type of cells in the tumour, and how they interact with breast cancer cells, can impact how the tumour responds to treatments. 

Esther and her team are interested in 2 types of cells found in the tumour – T cells and cancer-associated fibroblasts (CAFs). 

T cells are a type of immune cell that can identify and destroy cancer cells. But occasionally breast cancer can escape T cells and continue to grow. CAFs are a group of healthy cells, and some of them can help tumours grow.

So the team want to understand more about how these cells interact, and how the tumour can use CAFs to disarm T cells.

Esther and her team are focusing on 2 main projects:

1. Understanding which CAFs stop T cells from killing breast cancer 
   

   The researchers are studying triple negative breast cancer in mice. They’re comparing tumours that escape T cells and continue to grow and those that don’t. 

   The team want to understand what changes happen in the tumour microenvironment in each case. Using cutting-edge gene and protein analysis, they’re studying the differences in the types of CAFs in these tumours. 

   This will tell them which CAFs are disarming T cells. They then hope to find new drug targets for future treatments that stop these CAFs. This could allow T cells to work properly to kill breast cancer. 
   
   

2. Investigating how treatment impacts CAFs and T cells

   Cancer treatments can also change the tumour microenvironment. Some of these changes can allow the tumour to resist treatment, continue to grow and spread. So the team is investigating how treatment impacts the interactions between CAFs and T cells. 

   To do this, the researchers are growing mini triple negative breast cancer tumours in a dish in the lab, and mice, and treating them with chemotherapy and immunotherapy. They’re studying how the CAFs behave in the mini tumours that respond or resist treatment. And they’re measuring how it impacts the T cell's ability to kill breast cancer.

   The researchers hope that knowing which types of CAFs help triple negative breast cancer resist treatments could in the future help to predict treatment success.

   And they’ll also use this knowledge to target these CAFs to overcome resistance to standard treatments.

Esther’s research could help us understand how CAFs interact with T cells to help triple negative breast cancer grow and resist treatments. This could lead to new and more effective treatments for triple negative breast cancer.

Thousands. This research could find better treatments for the 8,000 people who are diagnosed with triple negative breast cancer each year in the UK.