A Small Amino Acid, Big Impact: Methionine Restriction in Cancer Therapy

A recent study published inGut(doi:10.1136/gutjnl-2022-326928) reveals a novel potential strategy for cancer immunotherapy: a methioninerestricted diet (MRD).A research team, led by Dr.JU Huaiqiang and Dr.XU Ruihua from the Sun Yat-sen University Cancer Center, and Dr.PIAO Hailong from the CAS Dalian Institute of Chemical Physics (DICP),discovered that a diet deficient in methionine, an essential amino acid, can reduce tumor growth and boost antitumor immunity.This is achieved by increasing the number and cytotoxicity of tumor-infiltrating CD8+T cells, a type of immune cell that plays a crucial role in fighting cancer.

In addition to the diet, the researchers also identified a critical player in anticancer immunity: a protein called YTHDF1.High expression of YTHDF1 was found to correlate with poor prognosis and less effective immunotherapy outcomes for cancer patients.The study suggests that either a methionine-restricted diet or YTHDF1 depletion can inhibit tumor growth and synergize with PD-1 blockade, a type of immunotherapy,for better tumor control.

Methionine, an essential amino acid in humans, after converting into S-Adenosylmethionine (SAM) acts as the methyl group donor in DNA or RNA methylation, a process that has given rise to the science of epigenetics.

“Methionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T cells,”the researchers explained.“Targeting methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy.”