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ImmunoFit SIGNED

Harnessing tumor metabolism to overcome immunosupression

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 ImmunoFit project word cloud

Explore the words cloud of the ImmunoFit project. It provides you a very rough idea of what is the project "ImmunoFit" about.

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Project "ImmunoFit" data sheet

The following table provides information about the project.

Coordinator
VIB 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Total cost 1˙999˙721 €
 EC max contribution 1˙999˙721 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2023-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB BE (ZWIJNAARDE - GENT) coordinator 1˙999˙721.00

Map

 Project objective

Anti-cancer immunotherapy has provided patients with a promising treatment. Yet, it has also unveiled that the immunosuppressive tumor microenvironment (TME) hampers the efficiency of this therapeutic option and limits its success. The concept that metabolism is able to shape the immune response has gained general acceptance. Nonetheless, little is known on how the metabolic crosstalk between different tumor compartments contributes to the harsh TME and ultimately impairs T cell fitness within the tumor. This proposal aims to decipher which metabolic changes in the TME impede proper anti-tumor immunity. Starting from the meta-analysis of public human datasets, corroborated by metabolomics and transcriptomics data from several mouse tumors, we ranked clinically relevant and altered metabolic pathways that correlate with resistance to immunotherapy. Using a CRISPR/Cas9 platform for their functional in vivo selection, we want to identify cancer cell intrinsic metabolic mediators and, indirectly, distinguish those belonging specifically to the stroma. By means of genetic tools and small molecules, we will modify promising metabolic pathways in cancer cells and stromal cells (particularly in tumor-associated macrophages) to harness tumor immunosuppression. In a mirroring approach, we will apply a similar screening tool on cytotoxic T cells to identify metabolic targets that enhance their fitness under adverse growth conditions. This will allow us to manipulate T cells ex vivo and to therapeutically intervene via adoptive T cell transfer. By analyzing the metabolic network and crosstalk within the tumor, this project will shed light on how metabolism contributes to the immunosuppressive TME and T cell maladaptation. The overall goal is to identify druggable metabolic targets that i) reinforce the intrinsic anti-tumor immune response by breaking immunosuppression and ii) promote T cell function in immunotherapeutic settings by rewiring either the TME or the T cell itself.

 Publications

year authors and title journal last update
List of publications.
2020 Carla Riera-Domingo, Annette Audigé, Sara Granja, Wan-Chen Cheng, Ping-Chih Ho, Fátima Baltazar, Christian Stockmann, Massimiliano Mazzone
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
published pages: 1-102, ISSN: 0031-9333, DOI: 10.1152/physrev.00018.2019
Physiological Reviews 100/1 2020-03-23
2019 Nina C. Flerin, Sotiria Pinioti, Alessio Menga, Alessandra Castegna, Massimiliano Mazzone
Impact of Immunometabolism on Cancer Metastasis: A Focus on T Cells and Macrophages
published pages: a037044, ISSN: 2157-1422, DOI: 10.1101/cshperspect.a037044
Cold Spring Harbor Perspectives in Medicine 15Oct2019 2020-03-23

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