Tracer-T · Analysis of the effect of the tumour microenvironment on T cell functional phenotype

Analysis of the effect of the tumour microenvironment on T cell functional phenotype

A successful adaptive immune response requires T cells to be able to adopt a specific metabolic phenotype. However, in diseases such as cancer or those associated with chronic inflammation, the metabolic microenvironment in which a T cell functions is likely to subvert this metabolic phenotype, thereby disrupting function. A better understanding of how the microenvironment affects T cell metabolism and function would permit the development of metabolic 'normalising' treatments that could restore function and permit disease resolution. The overall aim of Tracer-T was to identify how metabolites that build up in hypoxic tumour microenvironments impair T cell function, and whether this could be reversed to aid tumour cell killing. We planned to use parallel immunological and metabolic analyses, including stable isotope-based tracing approaches, to identify the the precise pathways involved. Subsequently, by inhibiting the metabolic pathway implicated, genetically, pharmacologically, or using physiologically relevant stimuli we would unequivocally link specific immunomodulatory metabolites with T cell function. The specific research objectives (ROs) of this project were: RO1: Identify novel hypoxia-induced metabolites that alter T cell function RO2: Determine the mechanism by which some of these metabolites impair T cell function RO3: Identify routes by which normal T cell function can be retained in hypoxic conditions

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз