Uncovering immunoediting strategies underlying malignant transformation in breast tissues

Breast cancer is the leading cause of cancer-related death in women worldwide. Despite intense research that has led to improved clinical outcomes, a significant number of patients treated with standard therapies suffer from high toxicity and remain unresponsive. In parallel, Immune-Checkpoint Inhibitors (ICI) have transformed cancer treatment by unleashing patients' immune system to combat cancer cells through immunoediting, a natural evolutionary process of removal of antigenic tumor clones. However, application of ICIs for breast cancer remains a challenge as we currently have limited knowledge of the immunoediting strategies and the mechanisms of immune evasion occurring in healthy and malignant tissues. We hypothesize that immunoediting shapes genetic heterogeneity and immunogenicity in healthy mammary cells, driving malignant transformation and response to clinical interventions. To test our hypothesis, we will investigate the mechanisms and influence of immune selection in mammary cells by exploiting novel genomic technologies, providing critical insight into the interplay between the immune system and breast cancer initiation. Our research project will focus on (1) exploring immune selection in healthy and premalignant breast tissues, (2) characterising immune cell populations and their spatial distribution, and (3) determining which interactions prevail during tumour progression. To achieve these goals, we will employ a combination of advanced molecular and high-throughput technologies, including laser microdissection, whole exome sequencing, RNA sequencing, and spatial transcriptomics.Our research has the potential to significantly advance our understanding of breast cancer occurrence and spread, ultimately leading to the development of novel prevention strategies, early detection methods, and personalised treatment approaches that harness the power of the immune system to fight more effectively breast tumorigenesis.