Autophagy Suppresses CD8+ T cell Anti-tumour Immunity
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ABSTRACT: Here we demonstrate that inactivation of the essential autophagy genes, Atg5, Atg14, or Atg16L1 results in tumour rejection. Despite a significant reduction in the total number of CD8+ tumour infiltrating lymphocytes (TILs), loss of Atg5 causes a profound shift toward IFNg and TNF producing effector memory cells. Consistent with this, adoptive transfer with Atg5-/- T cells promotes tumour control. Mechanistically, CD8+ T cells lacking autophagy exhibit enhanced glucose metabolism resulting in global changes in histone trimethylation and increased transcriptional activation of effector target genes. Restricting glucose is sufficient to suppress autophagy-dependent increases in effector function and reverse alterations in histone trimethylation. These findings identify autophagy as a cell-autonomous negative regulator of CD8+ T cell anti-tumour immunity with implications on T cell-based immunotherapy.
ORGANISM(S): Mus musculus
PROVIDER: GSE117757 | GEO | 2019/04/09
REPOSITORIES: GEO
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