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Myeloid Cells: Investigating their Role for Immunotherapy in Cancer

Descrizione del progetto

Il coinvolgimento delle cellule dendritiche nell’approccio dell’immunoterapia

L’attivazione del sistema immunitario per debellare il cancro rappresenta una strategia promettente che ha, tuttavia, dimostrato un’efficienza ridotta nella pratica clinica. Con l’obiettivo di migliorare l’esito dell’immunoterapia, gli scienziati del progetto MIRIC, finanziato dall’UE, propongono di coinvolgere le cellule mieloidi quali le cellule dendritiche, che svolgono un ruolo fondamentale nelle risposte delle cellule T antigene-specifiche e nella prognosi del cancro. MIRIC si soffermerà sul dominio dell’immunoglobulina delle cellule T e dominio della mucina 3 (TIM 3), un controllo immunitario responsabile dell’esaurimento delle cellule T e dell’inibizione dell’immunità antitumorale. Tramite l’impiego di tecnologie omiche e un approccio basato sul sistema immunitario, il progetto decifrerà l’esito della modulazione TIM 3 nel cancro, auspicandosi di fare luce sui fattori che regolamentano le risposte immunitarie durante la neoplasia.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

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

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-MSCA-IF-2020

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Coordinatore

UNIVERSITAT BASEL
Contributo netto dell'UE
€ 203 149,44
Indirizzo
PETERSPLATZ 1
4051 Basel
Svizzera
Regione
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 203 149,44