Descrizione del progetto
Interazioni immunitarie nel microambiente tumorale
Il sistema immunitario svolge un ruolo centrale nella progressione tumorale e negli esiti della malattia. Le prove accumulate indicano che due sottotipi di cellule immuni si infiltrano nel microambiente tumorale con ruoli opposti. Le cellule T γδ che producono l’interferone-γ possiedono un effetto antitumorale, mentre le cellule T γδ che secernono IL-17A supportano la crescita tumorale. Gli scienziati del progetto GammaDeltaTME, finanziato dall’UE, indagheranno i meccanismi alla base dell’equilibrio tra questi sottoinsiemi antagonisti di cellule T. A tal fine, essi analizzeranno le interazioni delle cellule immuni nel microambiente tumorale a livello metabolico, trascrittomico e epigenetico. I risultati del progetto possiedono il potenziale per incoraggiare strategie innovative per la promozione delle funzioni delle cellule T come intervento terapeutico.
Obiettivo
Immune cells constitute a major component of the tumor microenvironment (TME) that influence several aspects of cancer progression and outcome. The host laboratory has identified two distinct γδ T-cell subsets with opposing roles in tumor progression: whereas interferon-γ (IFN-γ)-producing γδ T-cells stimulate anti-tumor responses, IL-17A-secreting γδ T-cells promote angiogenesis and tumor growth. However, the cellular and molecular factors controlling the critical balance between these antagonistic subsets remain unknown.
The present proposal builds on subsequent relevant findings of the host laboratory, namely that neutrophils suppress IL-17A+ γδ T-cell proliferation, revealing an unanticipated neutrophil/γδ T-cell crosstalk in TME, and that on another side the metabolic resources may also play a critical role in γδ T-cell subsets.
Based on these foundations, within the present proposal we will:
a) identify TME cellular partners that determine the balance between IFN-γ+ and IL-17A+ γδ T-cells in several experimental models of cancer.
b) study the metabolic pathways employed by γδ T-cell subsets and the impact of manipulating those pathways on their balance within the TME
c) analyze the impact of immune crosstalk and metabolic resources on γδ T-cell subsets both at transcriptomic and epigenetic levels.
Overall, this project will provide conceptual advances that will foster innovative strategies to promote anti-tumor γδ cell functions at the expense of their pro-tumoral activities.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
1649 028 Lisboa
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