Project description
T cell mutations and anti-tumour activity
T lymphocytes vary considerably in their ability to infiltrate and attack tumours. However, the genetic factors underlying this variation are poorly understood. Emerging evidence suggests that naturally occurring mutations accumulating in T cell populations over time may actually enhance their anti-tumour activity. The ERC-funded tL-CHANCER project will investigate these mutations in cancer patients for the first time. Researchers will use large-scale genomic sequencing and advanced analytical tools to characterise how these variants influence T cell function and tumour infiltration. Overall, the project aims to unlock a new avenue for developing precision-engineered T cell therapies for solid tumours.
Objective
Cancer remains a global health crisis, with over 19 million new cases and 10 million deaths annually. Despite recent success, the efficacy of immunotherapies to treat solid tumors is still limited. T-lymphocytes, central to adaptive immunity, are key players in immunotherapy, yet their genetic heterogeneity and ability to infiltrate and respond effectively to tumors in treatment-naïve and treated patients remains poorly understood. This gap in knowledge presents a significant challenge to advancing cancer immunotherapy.
The main hypothesis of tL-CHANCER is that naturally occurring somatic mutations in T-lymphocyte expanded clones, known as T-Lymphocyte Clonal Hematopoiesis (tL-CH), enhance anti-tumor activity, offering a new approach to cancer treatment. By systematically investigating tL-CH mutations in cancer patients, I aim to uncover for the first time their impact on T-cell function, solid tumor infiltration dynamics, and anti-tumor immunity. My approach is original because it explores the uncharted landscape of tL-CH variants, rather than focusing on known T-cell mechanisms. Now is the ideal time to pursue this due to recent advancements in DNA sequencing and the growing recognition of the role of T-lymphocytes in cancer immunity. The project will leverage large-scale genomics and advanced analytical techniques to identify and characterize somatic variants in T-cells, providing insights into their functional impact on cancer immunity.
tL-CHANCER will revolutionize cancer immunotherapy by enabling the development of precision-engineered T-cell therapies based on tL-CH mutations. This research will advance our understanding of cancer evolution and create new therapeutic strategies, leading to more effective and personalized treatments for solid tumor patients. By integrating the genetic landscape of T-cells with their response to tumor-derived signals, the project will significantly impact cancer immunology and pave the way for future therapeutic innovations.
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.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- 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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HORIZON.1.1 - European Research Council (ERC)
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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.
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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-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2025-COG
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08035 Barcelona
Spain
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