Understanding how immune cells can influence treatment resistance in triple negative breast cancer

Triple negative breast cancer can be more aggressive than other types of breast cancer. Many people with triple negative disease are given chemotherapy and immunotherapy before surgery. And while this is often very effective, for some people it doesn’t work as well. When this happens, breast cancer is more likely to return in the future. 

To date, researchers mainly focussed on investigating a type of immune cell called T-cells and how they influence cancer’s response to treatments. But other immune cells known as B-cells and NK-cells may also play a key role. 

Understanding how these cells behave in people whose breast cancer doesn’t respond to treatment could help researchers find better treatments and stop cancer coming back. 

The researchers are studying how B-cells and NK-cells behave in people with triple negative breast cancer before, during and after treatment. They’re collecting blood, lymph node and tumour samples from patients diagnosed with triple negative breast cancer, and using advanced techniques to map how these immune cells interact with breast cancer cells.

By bringing together information from all these compartments, the team aims to build a complete picture of how the immune system responds.

They’re also running lab experiments, using 3D mini tumours grown in the lab, and working with specialised mice that allow the team to track how immune cells move in and out of tumours and lymph nodes in real time. They’re also investigating how immune cells interact with specially designed cancer-killing viruses, known as oncolytic viruses, and whether these can be used to re-train the immune system to fight cancer.

This combined approach will help uncover why existing immunotherapies sometimes fail to turn on the immune system against triple negative breast cancer, and how to overcome this.

Sheeba and her team are focusing on 3 projects:

1. Understanding how B-cells and NK-cells behave in people with triple negative breast cancer
   
   The team is collecting blood, tumour and lymph node samples from people with triple negative breast cancer who are having chemotherapy and immunotherapy. They’ll study how their B-cells and NK-cells behave at different stages of treatment. By comparing the differences in these immune cells between people whose breast cancer does and doesn’t respond to treatment, the team hopes to spot patterns that explain treatment resistance. 
   
   This will help reveal how the immune system changes in response to treatment and identify what might be happening in more aggressive, treatment-resistant cancers.
   
   
2. Mapping where immune cells are and how they interact with cancer cells
   
   The researchers are examining exactly where immune cells are located within tumours and lymph nodes, and how they interact with both cancer cells and other immune cells. Using cutting-edge imaging and analysis techniques, the team is creating detailed maps showing how B-cells and NK-cells are positioned in the tumour environment. They’ll compare these maps between people whose breast tumours do and don’t respond to treatment.
   
   In doing so, they hope to understand which immune patterns can better predict a positive response to treatment, and which ones allow the cancer to resist treatment.
   
   
3. Testing how to change immune cell behaviour in the lab
   
   The team is using 3D mini tumours grown in the lab, alongside mice that have tumours very similar to those found in treatment-resistant triple negative breast cancer in humans. The researchers are studying how B-cells and NK-cells behave in these environments and are testing ways to change them to target triple negative breast cancer more effectively. They are also investigating how immune cells interact with oncolytic viruses, and whether these can be used to re-train the immune system to fight cancer.
   
   By tracking how immune cells move and interact with the cancer in real time, they hope to uncover how resistance develops – and how it might be reversed to improve treatments.

This research hopes to improve our understanding of the interactions between triple negative breast cancer cells and immune cells. The researchers are also aiming to reveal new ways to help people whose breast cancer doesn’t respond to chemotherapy or immunotherapy.

This knowledge is essential for the development of new treatments that harness the body’s own immune system against breast cancer cells.

Every year in the UK, over 8,000 people are diagnosed with triple negative breast cancer. That’s 15% of all breast cancer diagnoses.