Breast cancer and high-grade serous ovarian cancer are leading causes of cancer-related death in women. For many families, these diagnoses are linked to inherited mutations, or mistakes, in the BRCA1 gene. This gene appears in every cell of the body and plays a critical role in repairing damaged DNA. Normally, cells carry two copies of the BRCA1 gene, so if one doesn’t function properly, the other can act as a backup. However, if additional mutations occur, this repair system can fail, allowing cancer to develop.
BRCA1-related cancers are aggressive and difficult to treat. They also share a puzzling feature compared with other tumours: they contain larger numbers of immune cells. This suggests the immune system recognizes the cancer and is gathering to destroy it – yet something prevents these immune cells from attacking the tumour. As a result, despite the presence of immune cells, BRCA1-related tumours do not respond better to immunotherapies than other cancers.
This raises an important question: Are the immune cells in the tumour failing to attack, or has the immune system been altered so that it helps, rather than hinders, these cancers?
With $525,000 in support from a Terry Fox New Investigator Award, made possible through funding by the River Philip Foundation, Dr. Hannah Garner, assistant professor at McGill University, will investigate why the immune system can’t kill BRCA1-related breast and ovarian tumours, and identify new ways to harness the immune system against these aggressive cancers.
“Our research aims to understand how these cancers interfere with the immune system, preventing it from recognizing and attacking tumour cells,” says Dr. Garner. “By finding ways to reverse these changes, we hope to help the immune system fight cancer more effectively.”
Her team will build on previous work showing that tumours can create a state of chronic, body-wide inflammation that alters the production and behaviour of immune cells that normally serve as a first line of defence against infection and disease. Under these conditions, these cells can be reprogrammed to suppress the immune response that would otherwise attack the tumour, supporting the cancer to growth and spread.
Over the next three years, they will examine how BRCA1 loss in cancer cells, combined with reduced BRCA1 function in the immune system, reshapes the body’s defences, and identify whether these changes are the same or different between BRCA1-associated breast and ovarian cancers.
Ultimately, this project aims to advance our understanding of how the immune system functions in female-specific cancers and identify actionable targets to guide more personalized and effective treatment strategies.
“I want to thank donors for their support, which makes it possible for scientists like me to ask bold questions, to build independent research programs and to pursue discoveries that may not be immediately obvious but have the potential to fundamentally change how we understand and treat cancer,” says Dr. Garner.
“This Terry Fox New Investigator Award fuels not only my research, but also my sense of responsibility to work with integrity, urgency and purpose toward a future where fewer patients and families are affected by cancer.”