Project description
Hidden immune changes and cancer relapse
Recurrence of cancer is a frequent phenomenon, even after the primary tumour has been surgically removed. Moreover, this relapse often coincides with the onset of metastatic disease. With the support of the Marie Skłodowska-Curie Actions programme, the TT-EPIC project is exploring the hypothesis that tumours induce long-lasting alterations in the immune system. The research team aims to elucidate the mechanisms by which tumours modulate bone marrow cells to become less effective at fighting cancer. Using melanoma as a model, the study will investigate how tumour signals permanently reprogramme these cells at the genetic and epigenetic level. The goal is to identify and reverse this immune dysfunction, offering new ways to prevent cancer relapse.
Objective
Despite successful surgical removal of primary tumors, many cancer patients ultimately succumb to metastatic relapse, often years after apparent cure. How tumors imprint long-lasting changes on the immune system that favor this deadly recurrence remains largely unknown. Tumors can epigenetically and transcriptionally reprogram bone marrow progenitors, establishing a “trained tolerance” state in myeloid cells that promotes immune evasion and metastasis. I hypothesize that tumor-derived factors induce long-lasting epigenetic and transcriptional reprogramming of bone marrow myeloid progenitors, establishing a state of Tumor-Trained Tolerance (TTT) that promotes systemic immune suppression and metastatic susceptibility even after complete removal of the primary tumor. Using melanoma as a clinically relevant model, I will dissect how tumor-induced reprogramming persists after tumor resection, identify the key molecular regulators, including MYC and epigenetic factors, and test whether these alterations can be reversed to restore immune vigilance. By integrating single-cell multi-omics (scRNA-seq, scATAC-seq, CITE-seq), proteomics, and targeted epigenetic profiling (histone marks and DNA methylation), I will map the regulatory networks underlying trained tolerance. Functional perturbations with CRISPR-based and pharmacological tools will determine causality and assess the potential to prevent metastasis. Finally, analysis of blood samples from melanoma patients will evaluate whether these signatures are conserved in humans, providing translational insight. This project combines cutting-edge molecular, computational, and in vivo approaches to reveal the hidden systemic consequences of primary tumors, aiming to uncover novel strategies to prevent the deadliest phase of cancer: metastatic relapse.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology skin cancer melanoma
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics epigenetics
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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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) HORIZON-MSCA-2025-PF
See all projects funded under this callCoordinator
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.
9052 ZWIJNAARDE - GENT
Belgium
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.