Project description
Insight into immunotherapy resistance in breast cancer
Triple-negative breast cancer (TNBC) represents the most aggressive and difficult-to-treat type of breast cancer. While new immunotherapies such as anti-PD1 antibodies have improved outcomes for some patients, they often cause serious immune-related side effects and resistance remains common. With the support of the Marie Skłodowska-Curie Actions programme, the Bio3XBRIT project will investigate how immune cells respond to immunotherapy in patients with TNBC. Researchers will analyse T-cell populations and tumour gene expression at the single cell level to identify biomarkers capable of predicting treatment response and toxicity. Project insights could lead to safer and more effective immunotherapy strategies for breast cancer.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine surgery
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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75231 Paris
France
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