Dissecting Cross-Regulatory Interplays in Tumor-Associated Macrophages

Informazioni relative al progetto

X-TAM

ID dell’accordo di sovvenzione: 759532

DOI

10.3030/759532

Progetto chiuso

Data della firma CE 24 Ottobre 2017

Data di avvio 1 Marzo 2018

Data di completamento 31 Agosto 2023

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 498 125,00

Contributo UE

€ 1 498 125,00

Coordinato da

OSPEDALE SAN RAFFAELE SRL
Italy

Periodic Reporting for period 4 - X-TAM (Dissecting Cross-Regulatory Interplays in Tumor-Associated Macrophages)

Periodo di rendicontazione: 2022-09-01 al 2023-08-31

Sintesi del contesto e degli obiettivi generali del progetto

Pancreatic cancer is one of the most aggressive forms of tumors, for which limited therapeutic options are available. The characterization of pathogenetic events in pancreatic cancer progression and the identification of novel therapeutic targets remain fundamental objectives in oncology. In this context, there is evidence that pancreatic cancer can subdue the host immune system by reprogramming the activity of a type of immune cells called macrophages. This project aimed at determining how pancreatic cancer interact with tumor-associated macrophages, with the goal of identifying actionable therapeutic targets to boosting anti-tumor immunity for the treatment of this disease.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Using cutting-edge genomic technologies, we have performed a comprehensive analysis of the molecular alterations occurring in cells of the immune system upon infiltration into pancreatic tumors. These data have revealed a unique molecular blueprint of tumor-associated macrophages that is associated to disease progression and poor prognosis. We have found that pancreatic cancer cells produce a class of molecules able to convert macrophages from activators to suppressors of anti-tumor immunity. In preliminary experiments, targeting these molecules was associated to reduced tumor growth and higher immune-mediated tumor rejection in preclinical models of pancreatic cancer. These studies have resulted in publications in major scientific journals and have been presented at international scientific meeting. Finally, results of the project were communicated nationally and internationally via social networks, press releases, and participation to radio broadcasts.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

This project combined innovative genomic technologies with advanced bioinformatic analyses to uncover novel drivers of pancreatic cancer progression and regulators of the interplay with the immune system. We have uncovered a novel therapeutic target - namely, a specific interplay between macropjahges and tumor cells - whose manipulation in experimental models efficiently limited tumor growth in vivo. These studies have major translational implications as they highlight a novel strategy to modulate immune dynamics in a disease largely resistant to immunotherapies.

Localized interaction between macrophages and tumor cells, fueling disease progression