Project description
Inhibition of tumour-associated macrophages as an anti-cancer treatment
Infiltration of tumour-associated macrophages (TAMs) is linked to poor cancer prognosis. Recent evidence indicates that inhibition of TAM migration reduces tumour infiltration and halts cancer progression in animal models. The EU-funded MacrophInt project proposes to target integrin signalling in TAMs as a new strategy to manipulate their infiltration into tumours. Integrins are central to the mesenchymal migratory mode of TAMs, which involves the adherence of cell podosomes to the surrounding extracellular matrix. Inhibition of TAM migration could be employed in conjunction with other anti-cancer strategies to improve patient clinical outcome.
Objective
Cancer is the most common cause of death and morbidity in Europe. New therapeutic targets to combat this disease are critical. Across many solid cancers, poor prognosis largely correlates with the infiltration of tumour-associated macrophages (TAMs). TAMs enhance tumour progression and complicate various anticancer therapies. Although macrophages primarily employ amoeboid migration for homeostasis and immune functions, TAMs primarily utilize mesenchymal migration. Experiments in mice revealed that blockade of TAM mesenchymal migration lowers infiltration within tumours and reduces tumour growth. Targeting this distinctive feature has the potential to limit TAM recruitment in tumours and halt disease progression, while preserving healthy macrophage functions. The mesenchymal migratory mode involves podosomes and is characterized by integrin-mediated adherence to the surrounding extracellular matrix (ECM), and the requirement of ECM proteolysis. In sharp contrast, amoeboid migration is independent of podosomes and integrins. We will investigate and evaluate the potential of targeting integrin signaling as a new strategy to manipulate TAM infiltration into tumours. Elegant knock-in and knockout mouse models will be used to establish the key regulators of integrin signaling in TAM mesenchymal migration. This novel paradigm will be extended to TAM migration in human breast tumour specimens. We will also provide new insights at the subcellular level by exploring the roles of integrin signaling in the formation and function of podosomes. Our study endeavours to identify novel and unanticipated avenues for blockade of TAM mesenchymal migration and tumour infiltration to synergize with current combination therapies that simultaneously target both pro-tumour stromal cells and cancer cells. Targeting mesenchymal migration in macrophages could have far-reaching implications beyond cancer in other disease contexts that involve macrophages including chronic inflammation.
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 physiology homeostasis
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-RI - RI – Reintegration panel
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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) H2020-MSCA-IF-2018
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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.
75794 PARIS
France
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.