Project description
Reprogramming T-cells to boost cancer immunotherapy
Immunotherapy fails for many patients because their T-cells lose their ability to fight tumours. The ERC-funded TREAT project aims to explore a middle-ground cell type known as the ‘intermediate exhausted’ T-cell, which can still respond to treatment and kill cancer cells. By combining CRISPR genetic screening with single-cell multiomics, the project expects to identify the exact signals that create these cells. By controlling these pathways, the project intends to reprogram exhausted T-cells into durable, protective states, significantly improving the performance of checkpoint inhibitors.
Objective
Cancer Immunotherapy has revolutionized Clinical Oncology. Yet, CD8 T-cell exhaustion remains a leading cause of treatment failure. This hypofunctional program suppresses anti-tumor CD8 T-cell responses and is reinforced by a stable epigenetic program that prevents exhausted CD8 T-cells (Tex) from reverting to more functional states. Checkpoint inhibitors such as anti-PD-1 can temporally relieve some constraints on TEX and be curative. However, this approach alone does overcome the epigenetic restraints of exhaustion which likely explains the lack of long-term benefits in many patients. Combinatorial approaches are needed to achieve durable protection in more patients. Yet, an incomplete understanding of TEX biology has provided little rationale for relevant therapeutic interventions.
Recent identification of an “effector-like” subset of TEX (TEX intermediate; TEXint) that mediates the benefits of PD-1 therapy and partially escapes the epigenetic strains of exhaustion, has brought new therapeutic perspective. Indeed, manipulating key pathways related to TEXint cells formation such as the IL-2/Stat5a axis potentiates TEX responses to PD-1 blockade and partially reprogram these cells towards more durably protective cell states. These findings provide compelling proof-of-concept that targeting key pathways driving Texint cell formation can unlock new strategies to overcome exhaustion and bolster PD-1 therapy.
Building on this novel concept, our proposal utilizes advanced murine models alongside molecular engineering, large-scale genetic perturbation tools (CRISPR), and single-cell multiomics to uncover and characterize new regulatory pathways for Texint cell development. Our goal is to unveil new strategies to improve PD-1 therapy and advance next-generation anti-cancer immunotherapies.
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
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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) ERC-2025-STG
See all projects funded under this callHost institution
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.
4051 Basel
Switzerland
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.