Project description
Immune crosstalk at the tumour microenvironment
The immune system plays a central role in tumour progression and disease outcome. Accumulating evidence indicates that two subtypes of immune cells infiltrate the tumour microenvironment with opposing roles. Interferon γ-producing γδ T cells have an anti-tumour effect, whereas IL-17A-secreting γδ T cells support tumour growth. Scientists of the EU-funded GammaDeltaTME project will investigate the mechanisms underlying the balance between these antagonistic T cell subsets. For this purpose, they will analyse the immune cell crosstalk in the tumour microenvironment at the metabolic, transcriptomic and epigenetic levels. The project's results have the potential to foster innovative strategies for promoting anti-tumour T cell functions as a therapeutic intervention.
Objective
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.
Fields of science
Keywords
Programme(s)
Topic(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
1649 028 Lisboa
Portugal