Killer immune cells in secondary triple negative breast cancer

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

Triple negative breast cancer lacks the proteins that are the target of many of the available targeted breast cancer treatments. And although therapies which use the immune system (immunotherapies) have changed the landscape of cancer treatment, they’re only effective in a small number of triple negative breast cancers.  

So we urgently need new ways to treat this type of breast cancer.  

The cells of the immune system protect us from infections and can even recognise and destroy some cancer cells. This knowledge has led to the development of immunotherapies to treat cancer. In a previous Breast Cancer Now project, Seth identified a type of immune cell which has the potential to be the target of an immunotherapy treatment for triple negative breast cancer.

The team found that this immune cell, called CD27 Ly6C gamma delta T (gdT) cells, were able to kill triple negative cancer cells in the lab. And in mice, they slowed the growth of the cancer and prevented secondary tumours developing in the lungs.  

Some gdT cell immunotherapies are already in development, but we need to better understand how gd T cells work to ensure that they’re as safe and effective as possible. So, Seth is now continuing his work to understand how gdT cells kill triple negative breast cancer cells. And how this could be used to develop new or better immunotherapies. 

In this project, Seth and his team will use advanced microscope techniques to visualise where gdT cells are located in lungs of healthy mice, in comparison to mice with breast cancer. This will help them understand how gdT cell location allows them to find incoming cancer cells in the lung.  

In their last project they found that gdT cells could destroy triple negative breast cancer cells in the lab dish. They want to expand on this work to understand how gdT cells kill the cancer cells. And they want to confirm gdT cell’s killing ability in mice with breast cancer. To do this, they’ll compare tumours in mice who have these gdT cells to those who have been engineered to lack them.  

Finally, Seth aims to identify ways that these gdT cells can be boosted using an immunotherapy treatment. To do this, the team will understand what proteins control their killing ability. They’ll use antibodies that target these proteins and test if the treatment increases how well gdT cells kill breast cancer cells in the lab. To understand how effective this treatment could be in the clinic, they’ll then test it on human gdT cells from donated samples from people with triple negative breast cancer.  

This project will tell us more about how gdT cells can find and destroy breast cancer cells. And if targeting them with immunotherapy could boost their ability to destroy triple negative breast cancer. If this project is successful, Seth believes that it will provide vital information to improve treatments for people with triple negative breast cancer. 

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

Breast Cancer Now thanks Secondary1st, secondary breast cancer research charity, for enabling this research with their generous support, covering the salary of the scientist carrying out this research project. The mission of Secondary1st is to raise awareness of and raise funds for research into secondary breast cancer. Find out more about Secondary1st at secondary1st.org.uk