Project description
Comprehensive study of specific T cell activity during breast cancer metastatic progression
Breast cancer is the second most common cancer in women. Improvement of the response of metastatic breast cancer to immunotherapeutic checkpoint blockade requires a better understanding of the particular immune landscape. Invariant natural killer T (iNKT) cells are specialised T cells that recognise lipid antigens. iNKT antitumour potential has been underinvestigated as they are scarcely present in cancer patients. The EU-funded BreaKer project works with the hypothesis that iNKT cells’ scarce presence and poor activation is a result of cancer-induced immunosuppressive mechanisms. The project objective is to carry out a comprehensive study of iNKT cell immunophenotype and activation mechanisms in metastatic breast cancer patients as well as healthy individuals to develop novel combinatorial immunotherapies for metastatic breast cancer.
Objective
Breast cancer is the second cause of cancer-related death in women. Although cancer immunotherapy emerged as a successful therapy for many cancer types, the response of metastatic breast cancer patients to immune checkpoint blockade remains disappointing, urging for a better understanding of the breast cancer immune landscape. iNKT cells are lipid-specific T cells that bridge innate and adaptive immunity and exert a plethora of immune functions depending on tissue distribution. Despite their known antitumor potential, they have been largely overlooked in the cancer field for their content paucity in cancer patients. I hypothesize that their scarce abundance and poor activation status is caused by cancer-induced immunosuppressive mechanisms. Indeed, I observed that circulating and metastasis-infiltrating iNKT cells are functionally impaired in the K14cre;Cdh1F/F;Trp53F/F(KEP)-based mouse model of de novo breast cancer metastases. With a translational approach, I will provide an unprecedented comprehensive dataset comparing iNKT cell immunophenotype in metastatic breast cancer patients and healthy controls. Next, I will generate human iNKT cell lines to perform in vitro mechanistic studies aimed at assessing how cancer-associated inflammation can modulate iNKT cell antitumor activity. Moreover, the innovative use of iNKT cell deficient Jα18-/- mice coupled to the KEP-based model of breast cancer metastases, will offer a clear picture of the role of iNKT cells and their cancer-associated cellular networks during the metastatic cascade. Finally, I will in vivo deplete immunosuppressive cells to unleash iNKT cell antitumor activity. My solid knowledge of iNKT cell biology combined with the expertise in breast cancer-associated inflammation of the hosting lab and the cutting-edge clinical research of the institute will uniquely generate fundamental knowledge with high applicative potential for the design of novel combinatorial immunotherapies for metastatic breast cancer.
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 oncology
- medical and health sciences basic medicine immunology immunotherapy
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Keywords
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1066 CX AMSTERDAM
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.