Modeling anti-tumor immune surveillance pathways at preneoplastic stage and resistance mechanism in advanced tumors to propose personalised treatment adaptation and innovation in TNBC

Breast Cancer (BC) is a major public health concern. Triple-negative BC (TNBC) have long been challenging to treat.

Pembrolizumab (anti-PD1) with neoadjuvant chemotherapy has recently become the standard of care in early TNBC, yet ~30% of patients resist and have poor outcome.

More effective immunotherapy (IT) strategies are needed.To address this, we will 1) validate biomarkers to identify patients that will not benefit from treatment, and 2) discover/validate alternative targets.The novelty and feasibility of the program reside in i) unique TNBC cohorts and already generated data with clinical information; ii) integrating innovative methodologies (scRNAseq, advanced spatial and computational biology) to identify biomarkers and resistance mechanism to IT and discover innate immune surveillance mechanisms that are overridden at preneoplastic stage; iii) validating novel targets and companion biomarkers, evaluating their impact on clinical outcome and exploring their biology in vivo/in vitro, iv) developing therapeutic antibodies against the validated targets, and v) involving clinicians and patients to validate the unmet medical need and facilitate transfer to care and acceptability of knowledge.The project relies on multidisciplinary and inter-sectorial collaborations between key opinion leaders, partners with expertise in TNBC clinical management, immuno-oncology, computational biology and clinical bioinformatics, drug development and patients and lay public interactions.