Cell Death and Immunity team

The immune system can detect and destroy breast cancer cells. But breast cancer can learn to hide from it, or manipulate the immune system into ignoring the tumour.

Treatments that direct the immune system against cancer cells are called immunotherapies. They are already used to treat some forms of breast cancer, but existing immunotherapies don’t work for everyone. We need to find better ways to flag up cancer cells to the immune system and turn on the immune system to destroy breast cancer cells.

Professor Pascal Meier and his team are looking for new ways to trigger the immune system to recognise and react against breast cancer.

They’re studying how the immune system is affected by the ways that cells die. We now know that cancer cells can die in very different ways, and depending on how they die they can release molecules that can turn on the immune response.

The researchers attempt to stimulate an immunogenic form of cell death so that the therapy triggers breast cancer cells to die in a way that teaches the immune system to identify the cancer. This could offer long-lasting protection against the disease.

Over 5 years, Pascal and his team will be focusing on 4 interlinked projects.

1. Investigating a type of cell death that stimulates the immune system
   RIP kinase is a protein that can direct cells to die in a way that draws the attention of the immune system. Pascal’s team want to find ways to use this protein against breast cancer. They are studying exactly how RIP kinase can turn on the immune system against cancer cells, and when it needs to be either suppressed or encouraged.

2. Finding ways to use existing breast cancer treatments to boost the immune response
   The researchers will be testing which types of cell death breast cancer tumours can choose. They’ll do this using mini-tumours, which are grown in the lab from tissue samples donated by people with breast cancer.
   
   Pascal and his team are also studying how tumours react to different treatments currently used for breast cancer, and how their responses can be re-wired to cause an anti-tumour immune response. This knowledge can be used to combine such therapies with immunotherapies to boost their effectiveness.

3. Looking for ways to make breast cancer cells more sensitive to drugs
   A key problem in treating breast cancer patients is that cancer cells frequently grow resistant to a type of cell death called apoptosis, causing treatments to fail. Pascal now has discovered a new way to kill such apoptosis-resistant cancer cells. This form of cancer cell death is different to apoptosis, and hence can even kill hard-to-treat breast cancer cells.
   
   By killing cancer cells in this new way, a patient’s own immune system will spring to action, thinking that the body is under virus attack. Using this strategy, Pascal’s team not only can kill apoptosis-resistant tumour cells but also wake-up a patient’s own immune system to attack and destroy the tumour and any cancer that has migrated to secondary sites.

4. Developing new treatments
   Cancer cells can take advantage of the way normal cells work, to destroy healthy cells around them. This is called super-competitor behaviour. The cells killed in this way by their neighbours are known as losers. Pascal and his team are studying how breast cancer cells do this, and want to find ways to use this super-competitor behaviour against them. Pascal wants to find treatments that could turn the super-competitor breast cancer cells into the loser cells and eliminate them.

Pascal and his team hope that this research will lead to better treatments for breast cancer, and reduce the chance of recurrence. Their work could find ways to make a person’s own immune system recognise and get rid of any remaining breast cancer cells after treatment. This could provide long-term protection against the disease coming back after treatment.