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- Abnormal epigenetic patterns is associated with effector T cell malfunction in tumors, but the cause of this correlation is unclear.
- Methionine is an amino acid that is a component of most proteins, and it is an essential nutrient in the diet of vertebrates.
- CD8+ T cell is a T lymphocyte that kills cancer cells.
- The study show that tumor cells alter methionine metabolism in CD8+ T cells.
- The alteration includes lowering the intracellular levels of methionine inside the cells.
- The alteration also includes lowering the intracellular levels of methyl donor S-adenosylmethionine (SAM).
- The result of these alteration is the loss of dimethylation at lysine 79 of histone H3 (H3K79me2).
- Loss of H3K79me2 resulted in low expression of STAT5 and impaired T cell immunity.
- STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes.
- Mechanistically, tumor cells enthusiastically consumed methionine and outcompeted T cells.
- Tumor cells compete with T cell for methionine by expressing high levels of the methionine transporter.
- Genetic and biochemical inhibition of tumor methionine transporter restored H3K79me2 in T cells, as a result boosting spontaneous and checkpoint-induced tumor immunity.
- In addition, methionine supplement improved the expression of H3K79me2 and STAT5 in T cells.
- The improvement due to methionine supplementation went along with increased T cell immunity in tumor-bearing mice and patients with colon cancer.
- Clinically, tumor methionine transporter has a negative correlation with T cell histone methylation and functional gene signatures.
- The study identify a physical connection between methionine metabolism, histone patterns, and T cell immunity in the tumor micro-environment.
- Cancer methionine consumption can be an immune evasion mechanism.
- The study suggests that targeting cancer methionine signalling is a potential cancer therapy.
Sources:
https://doi.org/10.1038/s41586-020-2682-1
https://languages.oup.com/google-dictionary-en/
https://doi.org/10.1016%2Fb978-0-12-817572-9.00007-0
https://doi.org/10.1093%2Femboj%2F18.17.4754
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The Chromoscience uses AI-assisted tools to support the preparation and editing of science articles. Content is reviewed by the editor for clarity and consistency with the cited research before publication. Readers are encouraged to consult the original scientific publications for complete findings, methods, and limitations.
