IMMUNOPREVENT · Leveraging the immune system for breast cancer prevention

Damaged cells, including precancerous cells, continuously accumulate in healthy tissues, but they are identified and eliminated by the immune system in a continuous process named immunosurveillance. Therefore, effective immunosurveillance plays an essential role in preventing cancer development. IMMUNOPREVENT aims to understand how aberrant precursor breast cancer cells escape from immune surveillance, and whether we can leverage this knowledge for future cancer prevention strategies for women at high risk of developing breast cancer. Mutations in the DNA repair genes BRCA1 and BRCA2 confer a 70% lifetime risk of breast cancer, in contrast to the 13% risk in the general female population. The majority of BRCA mutations are inherited, but there are no effective breast cancer prevention options for BRCA carriers besides the invasive prophylactic mastectomy. Therefore, this is an unmet clinical need that demands new knowledge that can be translated into prevention strategies in the future. In this project, I will investigate the potential tumour protective role of LCOR in clearing BRCA-deficient cancer-initiating cells before tumour establishment. LCOR enhances tumour immunogenicity by inducing tumour antigen presentation, thus rendering breast cancer cells visible and vulnerable to immune attack. However, its role in early oncogenesis remains unknown. Here, employing a novel mouse model for mammary gland-specific loss of Lcor and Brca1, I will interrogate the role of LCOR in premalignant clonal dynamics, tumour development and early immune evasion. This knowledge will expand our general understanding of the early immune-mediated events in the premalignant mammary gland that eventually lead to cancer initiation. With this fellowship I will gain skills and knowledge on immune oncology and the results generated will be the foundation for future research lines on immunotherapy for breast cancer prevention that I will pursue as an independent researcher.