Metabolic reprogramming reverses T-cell exhaustion in solid tumour microenvironments

Abstract

Exhausted CD8+ T cells limit the efficacy of checkpoint blockade in many solid tumours. Using single-cell transcriptomics and metabolic flux analysis, we identify a mitochondrial bottleneck that marks terminally exhausted populations. Pharmacological restoration of fatty-acid oxidation rescued effector function ex vivo and improved tumour control in combination with anti-PD-1 therapy in murine models.

Keywords

• immunotherapy
• T-cell exhaustion
• metabolism
• oncology