Project description
Inducing lymphoid structures for enhanced cancer immunotherapy
Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues formed at sites of persistent or chronic inflammation, including some tumours. Although TLS presence has been associated with improved prognosis and better response to immunotherapy, not all patients develop these immune structures. With the support of the Marie Skłodowska-Curie Actions programme, the TLSaRNA project aims to investigate novel therapies to induce TLS through intratumoural mRNA injection. The working hypothesis is that TLS may have a synergistic effect with immunotherapy. Moreover, the study will employ advanced techniques to uncover the role of tumour-specific B cells and antibodies.
Objective
Tertiary lymphoid structures (TLS) are ectopically generated lymphoid structures with some level of cellular organisation similar to the secondary lymphoid organs, characterised by having a B-cell zone adjacent to a T-cell zone. The presence of tumor immune infiltrates, especially in the form of TLS, has been linked to a better cancer prognosis in different types of tumor and improved response to immune checkpoint inhibitors (ICB). However, interestingly, not all the patients develop TLS and the cellular composition and organisation within the structures can vary. Specifically, the role of B cells in the tumor microenvironment is controversial, while some studies have reported a pro-tumoral effect, possibly through differentiation of regulatory B cells, metadata shows a strong association between the presence of a transcriptional B cell profile on the tumors and the improved patient outcome. Moreover, the presence of B cells in the tissue microenvironment is also positively associated with an improved response to ICB. However, even though these strong statistical associations and the relevance of TLS in the cancer prognosis, still little is known about the mechanisms underlying their function and the specific role of B cells in the anti-tumoral response elicited. In this proposal, we will study novel therapies for artificial TLS induction by using intratumoral injection of mRNAs encoding for specific cytokines. We will deeply characterise the synergy between immunotherapy treatments and TLS in the tumor development by using the state-of-the art spatial transcriptomics and immunophenotyping. Finally, we will decipher the function of tumor-specific B cells on the tumor microenvironment and the relevance of tumor-specific secreted antibodies in the overall anti-tumoral response. Ultimately, the knowledge generated with this proposal will provide relevant information to guide future immunotherapy treatments.
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.
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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31008 Pamplona
Spain
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