Titolo progetto: PRIN 2017 - Cell plasticity of tumor-associated immune infiltrate: molecular mechanisms and therapeutic options

Programma di finanziamento: PRIN: progetti di ricerca di rilevante interesse nazionale – Bando 2017

Responsabile scientifico: prof. Carlo Ennio Michele Pucillo

Ruolo del DAME: partner

Descrizione generale:

In the last decade chronic inflammation has emerged as a major driver of cancer development. Inflammatory bowel diseases represent the most clinically relevant example of inflammation preceding cancer development, as patients affected by ulcerative colitis and Crohn’s disease have a significant increased risk to develop colorectal carcinoma, which, despite improvements in early diagnosis and treatment, remains the fourth most common cause of death. In the last deaced a growing body of evidence has also clearly demonstrated the enormous anti-tumoral potential of immune cells. This apparent paradox is caused by the profound influence that the tumor microenvironment has on phenotypic and functional properties of tumor[1]associated innate cells of myeloid and lymphoid lineages as well as cells of the adaptive immunity. Taking advantage of their ability to adopt different functional profiles in response to environmental cues, a process usually alluded to as leukocyte plasticity, the tumor microenvironment in fact suppresses the anti-tumor potential and enhances the pro-tumor activities of virtually all different leukocyte subsets, thus corrupting immune cells to promote tumor escape and immunosuppression. Deciphering the genetic/epigenetic molecular mechanisms driving heterogeneity and plasticity of the tumor-associated immune infiltrate has potentially profound implications for the development of novel and more targeted therapeutic strategies, as reactivating an appropriate immune response to the tumor is a key determinant for response to therapy.

Genetic/epigenetic mechanisms are driving elements of heterogeneity and plasticity of the tumor-associated immune infiltrate, which in turn is a key determinant for response to therapy. Our ambition is to define the molecular pathways converting both the adaptive and innate branches of the immunity towards a pathogenic phenotype to develop strategies aimed at “re-educating” immune cells towards an anti-cancer phenotype.

Partner del progetto:

• Università degli Studi di Milano
• Università degli Studi di Firenze
• Università degli Studi di Roma “La Sapienza”
• Università degli Studi di Udine
• Università degli Studi di Verona
• HUMANITAS University

Date inizio e fine progetto: 27/09/2019 - 25/09/2023

Budget totale del progetto: 194.984,00 €

Sito web: www.miur.gov.it