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TNT-TUMORS SIGNED

Therapeutic approaches to enhance innate immunity against Tumors

Total Cost €

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EC-Contrib. €

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Partnership

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 TNT-TUMORS project word cloud

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

modulation    validated    cancer    subset    interesting    tams    expressing    tumorigenesis    inducible    immunetherapy    cell    fight    cooperation    activated    capacity    strategies    tam    ensures    reevaluate    immune    specificity    dendritic    immunemodulatory    never    power    endowing    innate    poorly    egfr    screens    patients    instructed    close    macrophages    harness    clinicians    fast    vitro    significance    therapeutic    samples    treatment    anti    pdcs    mimicking    mechanisms    utilize    drugs    metastasis    tumorigenic    plan    therapies    cells    inhibitors    restrained    immunemodulation    phenotype    types    recognition    molecularly    standard    attack    human    mouse    start    cancers    tumors    checkpoint    direct    plasmacytoid    molecular    models    clinical    dissect    independent    translation    occurs    platform    rnai    adaptive    recent    tumor    completely    first    mechanism    shows    killing    predictive    vivo    capacities    genetic    effect    look    interaction    possibility   

Project "TNT-TUMORS" data sheet

The following table provides information about the project.

Coordinator
MEDIZINISCHE UNIVERSITAET WIEN 

Organization address
address: SPITALGASSE 23
city: WIEN
postcode: 1090
website: www.meduniwien.ac.at

contact info
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name: n.a.
surname: n.a.
function: n.a.
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 Coordinator Country Austria [AT]
 Project website https://krebsforschung.meduniwien.ac.at/forschung-research/research-focuses/cellular-and-molecular-tumor-biology/maria-sibilia/
 Total cost 2˙499˙646 €
 EC max contribution 2˙499˙646 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MEDIZINISCHE UNIVERSITAET WIEN AT (WIEN) coordinator 2˙499˙646.00

Map

 Project objective

Recent advances using immune checkpoint inhibitors demonstrate the great potential of immunemodulation in cancer and metastasis treatment. However, the effective treatment of only a subset of patients shows that this is only the start to utilize the power of the immune system to fight cancer. An interesting approach is to harness innate immune cells, such as plasmacytoid dendritic cells (pDCs) and tumor-associated macrophages (TAM) to attack tumors and to enhance the effect of standard anti-cancer therapies. Recently, using mouse models we identified two independent mechanisms by which modulation of these two cell types restrained tumor growth. First, the direct killing of tumor cells by pDCs that occurs independent of the adaptive immune system. Second, we identified a tumor-promoting role of EGFR-expressing (EGFR) TAMs during tumorigenesis. This enables us to look at the role of EGFR in tumorigenesis in a completely new way and we plan to exploit this novel finding to reevaluate the mechanism by which anti-EGFR drugs are effective in tumors. The mechanisms endowing pDCs with tumor-killing capacities and determining the specificity of tumor cell recognition by activated pDCs are poorly understood. Furthermore, the interaction of pDCs with macrophages has never been investigated in tumors. Here I propose to define the molecular mechanisms by which pDCs and TAMs can be instructed to adopt an anti-tumorigenic phenotype. Inducible and cell-specific genetic mouse models mimicking human cancers will allow to molecularly dissect the immunemodulatory capacity of pDCs and TAMs. State-of-the-art large scale in vitro and in vivo RNAi screens will provide a platform to identify novel molecular pathways and open the possibility for testing new strategies in cancer immunetherapy. The clinical significance of our findings will be validated in human cancer samples in close cooperation with clinicians, which ensures a fast predictive and therapeutic translation of our results.

 Publications

year authors and title journal last update
List of publications.
2017 Sriram Srivatsa, Mariel C. Paul, Claudia Cardone, Martin Holcmann, Nicole Amberg, Paulina Pathria, Michaela A. Diamanti, Markus Linder, Gerald Timelthaler, Hans P. Dienes, Lukas Kenner, Fritz Wrba, Gerald W. Prager, Stefan Rose-John, Robert Eferl, Giuseppina Liguori, Gerardo Botti, Erika Martinelli, Florian R. Greten, Fortunato Ciardiello, Maria Sibilia
EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients
published pages: 178-190.e10, ISSN: 0016-5085, DOI: 10.1053/j.gastro.2017.03.053
Gastroenterology 153/1 2020-04-08
2018 Markus Linder, Elisabeth Glitzner, Sriram Srivatsa, Latifa Bakiri, Kazuhiko Matsuoka, Parastoo Shahrouzi, Monika Dumanic, Philipp Novoszel, Thomas Mohr, Oliver Langer, Thomas Wanek, Markus Mitterhauser, Erwin F Wagner, Maria Sibilia
EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling
published pages: e9408, ISSN: 1757-4676, DOI: 10.15252/emmm.201809408
EMBO Molecular Medicine 10/11 2020-04-08
2018 Stefanie Schmidt, Neele Schumacher, Jeanette Schwarz, Simone Tangermann, Lukas Kenner, Michaela Schlederer, Maria Sibilia, Markus Linder, Annelore Altendorf-Hofmann, Thomas Knösel, Elisabeth S. Gruber, Georg Oberhuber, Julia Bolik, Ateequr Rehman, Anupam Sinha, Juliane Lokau, Philipp Arnold, Anne-Sophie Cabron, Friederike Zunke, Christoph Becker-Pauly, Adele Preaudet, Paul Nguyen, Jennifer Huynh, Shoukat Afshar-Sterle, Ashwini L. Chand, Jürgen Westermann, Peter J. Dempsey, Christoph Garbers, Dirk Schmidt-Arras, Philip Rosenstiel, Tracy Putoczki, Matthias Ernst, Stefan Rose-John
ADAM17 is required for EGF-R–induced intestinal tumors via IL-6 trans-signaling
published pages: 1205-1225, ISSN: 0022-1007, DOI: 10.1084/jem.20171696
The Journal of Experimental Medicine 215/4 2020-04-08
2018 Markus Linder, Manfred Hecking, Elisabeth Glitzner, Karin Zwerina, Martin Holcmann, Latifa Bakiri, Maria Grazia Ruocco, Jan Tuckermann, Georg Schett, Erwin F. Wagner, Maria Sibilia
EGFR controls bone development by negatively regulating mTOR-signaling during osteoblast differentiation
published pages: 1094-1106, ISSN: 1350-9047, DOI: 10.1038/s41418-017-0054-7
Cell Death & Differentiation 25/6 2020-04-08

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