Myeloid-derived itaconate suppresses cytotoxic CD8⁺ T cells and promotes tumour growth.

ABSTRACT: The tumour microenvironment possesses mechanisms that suppress anti-tumour immunity. Itaconate is a metabolite produced from the Krebs cycle intermediate cis-aconitate by the activity of immune-responsive gene 1 (IRG1). While it is known to be immune modulatory, the role of itaconate in anti-tumour immunity is unclear. Here, we demonstrate that myeloid-derived suppressor cells (MDSCs) secrete itaconate that can be taken up by CD8⁺ T cells and suppress their proliferation, cytokine production and cytolytic activity. Metabolite profiling, stable-isotope tracing and metabolite supplementation studies indicated that itaconate suppressed the biosynthesis of aspartate and serine/glycine in CD8⁺ T cells to attenuate their proliferation and function. Host deletion of Irg1 in

SUBMITTER: Zhao H 

PROVIDER: S-EPMC10593361 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature