Therapeutic approaches to enhance innate immunity against Tumors

Projektinformationen

TNT-TUMORS

ID Finanzhilfevereinbarung: 694883

DOI 10.3030/694883

Abgeschlossenes Projekt

EK-Unterschriftsdatum 27 Juli 2016

Startdatum 1 September 2016

Enddatum 31 August 2022

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 2 499 646,00

EU-Beitrag € 2 499 646,00

Koordiniert durch

MEDIZINISCHE UNIVERSITAET WIEN
Austria

Ziel

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.

Wissenschaftliches Gebiet

• medical and health sciences › clinical medicine › oncology › colorectal cancer
• medical and health sciences › basic medicine › immunology › immunotherapy
• medical and health sciences › clinical medicine › gastroenterology

Schlüsselbegriffe

• TNT-TUMORS

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-ADG-2015 - ERC Advanced Grant

Aufforderung zur Vorschlagseinreichung

ERC-2015-AdG

Finanzierungsplan

ERC-ADG - Advanced Grant

Gastgebende Einrichtung

MEDIZINISCHE UNIVERSITAET WIEN

• Netto-EU-Beitrag: € 2 499 646,00
• Adresse: SPITALGASSE 23 ; 1090 Wien ; Österreich
• Region: Ostösterreich › Wien › Wien
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 2 499 646,00

Begünstigte (1)

MEDIZINISCHE UNIVERSITAET WIEN

Österreich

• Netto-EU-Beitrag: € 2 499 646,00
• Adresse: SPITALGASSE 23 ; 1090 Wien
• Region: Ostösterreich › Wien › Wien
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 2 499 646,00