Objective
Breast cancer remains a major public health issue, being the leading cause of cancer deaths among women in France, with around 58,459 new cases and 12,146 deaths reported in 2018. There are three main types: hormone receptor (HR)-positive (75-80% of cases), HER2-positive (15% of cases), and triple-negative breast cancer (TNBC) (15-20% of cases).
Standard treatment involves surgery, radiotherapy, chemotherapy, hormone therapy for HR-positive cases, and targeted anti-HER2 therapy for HER2-positive cases. Recently, immunotherapies like pembrolizumab (an anti-PD1 antibody) have been approved for TNBC patients, in combination with chemotherapy. However, immune checkpoint inhibitors are associated with immune-related adverse events (irAEs) due to generalized lymphocyte activation, which can affect any tissue and even lead to death in severe cases.
There is an urgent need to better understand the anti-tumor immune response to reduce toxicity, improve immuno-oncology strategies for TNBC, and broaden their application to other breast cancer types. Additionally, treatment resistance is a significant challenge, with unknown reasons limiting the number of patients achieving complete response.
The proposed project aims to advance breast cancer immunotherapy by developing a comprehensive molecular approach to discover TNBC immunotherapy biomarkers of treatment resistance and irAE development, thank to the access to TNBC patient cohorts.
Molecular characteristics and clonotype dynamics of T cells (CD8+, CD4+ Tconvs, and Tregs) at the single-cell level during anti-PD1 treatment, will be correlated with tumor transcriptomic data and clinical data. Analysis of an existing cohort of 83 TNBC patients treated with pembrolizumab and neoadjuvant chemotherapy will uncover aspects of the anti-tumor T-cell response, T-cell specificity, and identify novel biomarkers of resistance and toxicity, as well as targets for therapeutic options.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesclinical medicinesurgery
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
75231 Paris
France