Metabolic profiles of regulatory T cells in the tumour microenvironment

Metabolic reprogramming of cancer cells generates a tumour microenvironment (TME) characterised by nutrient restriction, hypoxia, acidity and oxidative stress. While these conditions are unfavourable for infiltrating effector T cells, accumulating evidence suggests that regulatory T cells (Tregs) continue to exert their immune-suppressive functions within the TME. The advantages of Tregs within the TME stem from their metabolic profile. Tregs rely on oxidative phosphorylation for their functions, which can be fuelled by a variety of substrates. Even though Tregs are an attractive target to augment anti-tumour immune responses, it remains a challenge to specifically target intra-tumoral Tregs. We provide a comprehensive review of distinct mechanistic links and pathways involved in regulation of Treg metabolism under the prevailing conditions within the tumour. We also describe how these Tregs differ from the ones in the periphery, and from conventional T cells in the tumour. Targeting pathways responsible for adaptation of Tregs in the tumour microenvironment improves anti-tumour immunity in preclinical models. This may provide alternative therapies aiming at reducing immune suppression in the tumour.

Automated summary

Metabolic reprogramming in cancer cells leads to the formation of a tumour microenvironment characterized by nutrient restriction, hypoxia, acidity, and oxidative stress, unfavorable for effector T cells but conducive for immune-suppressive functions of Tregs. Tregs rely on oxidative phosphorylation for their functions and have metabolic adaptations in the tumour microenvironment. Targeting pathways responsible for Tregs' adaptation in the tumour microenvironment can improve anti-tumour immunity in preclinical models.