Research Highlights: Cancer Cell Outcompetes T Cell in Methionine Consumption


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T cells attacking cancer cells. Credit: Prasad Adusumilli

Original Article: https://doi.org/10.1038/s41586-020-2682-1

  • 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.

Source:

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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Keywords: cancer therapy, cancer cure, cancer treatment, cancer immunotherapy, how cancer cell affect t cell, t cell, immune system, immunity

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