Objective
Colorectal cancer (CRC) is the second most common cause of cancer death with an alarming rising incidence among young individuals. While the management of early-stage CRC has improved greatly, the median overall survival for patients with metastatic CRC is 30 months. Immune checkpoint inhibitors (ICI) have revolutionized the treatment of advanced solid cancers, yet for CRC continue to lag behind, with the exception of 4% of patients with microsatellite instability. In contrast, several studies have shown limited to no clinical activity of ICI in microsatellite stable (MSS) CRC. A number of clinical trials with drug combinations have been caried out to convert “immune cold” into “immune hot” tumors. However, the objective response rates were disappointingly low. Thus, novel therapeutic concepts are required to improve outcome in MSS CRC patients.
We recently built a large-scale single-cell atlas of the CRC tumor microenvironment (TME) and showed remarkable heterogeneity, representing a major challenge in disease management, since patients with the same tumor subtype can have different immunotherapy responses. Moreover, we identified a subset of neutrophils, the most abundant leukocytes in the blood and highly enriched in the CRC TME, that could fuel ICI response. I propose to fill the knowledge gaps on the neutrophil diversity and function in MSS CRC using cutting-edge single-cell techniques and deep learning methods. We aim to: 1) chart multi-omics single-cell neutrophil map of the bone marrow-tumor axis; 2) identify neutrophil cell niches using samples from an ICI clinical trial and spatial single-cell transcriptomics; 3) relate neutrophil cell niches to clinical correlates using a large biobank and spatial single-cell proteomics; and 4) perform mechanistic studies using patient-derived tumor fragments and mouse models. The knowledge gain will lead to rationale for novel therapeutic framework that exploits anti-tumor strategies of the innate and adaptive immunity.
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.
This project's classification has been validated by the project's team.
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.
This project's classification has been validated by the project's team.
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-2024-ADG
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.
6020 Innsbruck
Austria
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.