Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0699790 (
colon cancer
)
28,837
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours
1-4
, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8
+
T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2 led to low expression of STAT5 and impaired T cell immunity. Mechanistically, tumour cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter
SLC43A2
. Genetic and biochemical inhibition of tumour
SLC43A2
restored H3K79me2 in T cells, thereby boosting spontaneous and checkpoint-induced tumour immunity. Moreover, methionine supplementation improved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunity in tumour-bearing mice and patients with
colon cancer
. Clinically, tumour
SLC43A2
correlated negatively with T cell histone methylation and functional gene signatures. Our results identify a mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumour microenvironment. Thus, cancer methionine consumption is an immune evasion mechanism, and targeting cancer methionine signalling may provide an immunotherapeutic approach.
...
PMID:Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. 3287 89
