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Myeloid Cells: Investigating their Role for Immunotherapy in Cancer

Project description

Involving dendritic cells in the immunotherapy approach

Activation of the immune system to tackle cancer is a promising strategy that has, however, demonstrated limited efficacy in clinical practice. To improve immunotherapy outcome, scientists of the EU-funded MIRIC project propose to engage myeloid cells such as dendritic cells which have a key role in antigen-specific T cell responses and cancer prognosis. MIRIC will focus on T-cell immunoglobulin mucin-3 (TIM-3), an immune checkpoint responsible for T-cell exhaustion and inhibition of antitumour immunity. Using omics technologies and a systems immunology approach, the project will decipher the outcome of TIM-3 modulation in cancer, hoping to shed light on the factors that govern immune responses during malignancy.

Objective

With more than 3.7 million new cases and 1.9 million deaths each year, cancer represents the second most important cause of death and morbidity in Europe with the estimated direct health cost increasing from €79 to €86 billion during 2005-2014. The emerging field of immune-checkpoint therapy (ICT) has demonstrated unprecedented responses in patients with several types of metastatic tumors that were previously resistant to available treatment options. However only ~13% of patients respond to the immunotherapy. I believe the primary reason for this is that most therapies are T cell directed and to achieve durable responses one must also engage the innate arm of the immune system. Myeloid cells constitute a major proportion of tumor infiltrating cells in human cancers and are essential for the induction of antigen specific T cell responses-cells which mediate anti-tumor immunity. Tim-3 is a check-point molecule that is not only expressed on T cells but also constitutively expressed on Dendritic cells, namely DC1, which are particularly adept at initiating protective anti-tumour immunity. A number of studies have highlighted the crucial role of DCs including analyses of The Cancer Genome Atlas showing that patient survival for many cancers correlates positively with the gene expression signature for DCs. Given the current activity in developing Tim-3 blocking agents for clinical translation, it is imperative that we have a full understanding of how modulation of Tim-3 affects the innate arm of the immune system. The aim of this proposal is to determine the cell-intrinsic and non cell-intrinsic effects of Tim-3 modulation in cancer. Furthermore we will analyze the cellular and transcriptional changes associated with tumour infiltrating DC after ICT with anti-Tim3. This proposal is highly interdisciplinary implementing single-cell 'omics' strategies and systems immunology approaches to further unravel the players and rules governing immune responses during malignancy.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

UNIVERSITAT BASEL
Net EU contribution

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.

€ 203 149,44
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 203 149,44
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