Nature: Finally know why cancer cells are so "big", it turns out that they are more "grabbing food"

If the body's immunea "line of defense" against invasion by "foreign enemies", then T-cells are the "number one killer".
, however, that this "powerful army" that is so large in the blood of the human body often does not work in the fight against cancer.
article published in Nature on September 2nd, local time, revealed new mechanisms of cancer immune escape.
A team at the University of Michigan points out that an amino acid called methionine has the greatest effect on the vitality and function of T cells, as tumor cells are better at "grabbing" the nutrient than T cells, resulting in lower levels of methionine in T cells, which in turn alters the modification pattern of histones and ultimately leads to impaired T-cell function.
methionine, general nail thioionine, is one of the essential amino acids that make up the human body and participates in protein synthesis.
substance cannot be self-synthetic in the human body, it must be obtained externally.
previous study of animal models of immunodeficiency suggests that tumor cells may be "obsessed" with methionine and suggests treatments for "starving" tumor cells by depriving methionine.
, this study suggests that this approach may be a double-edged sword.
study, researchers first conducted a study of T-apoptosis and found that the absence of methionine led to the most significant T-cell death and dysfunction.
In further analysis, the researchers tested whether tumor cells impaired CD8 T cell function by altering methionine levels, and showed that tumor cells significantly outstod T cells in ingestion of methionine, resulting in impaired T-cell function.
In order to study the mechanism by which tumor cells affect CD8 T cells through methionine deprivation, the researchers sequenced RNA with fresh mediums, liquid on melanoma cells, and CD8 T cells cultured with liquid on tumor cells, and found that in CD8 T cells cultured with liquid on tumor cells, there was a defect in the metabolic process and methionine circulation, and methionine supplementation could restore the process.
further analysis showed that tumor cells reduced methyl supply SAM by limiting methionine, thereby impairing histoprotein H3K79 dmylation (H3K79me2) in CD8 T cells and signal transductor and transcription activation factor 5 (STAT5) signals.
tumor cells alter the metabolism of CD8-T cell methionine, reducing H3K79me2 methionine is transported to cells through the solute vector family (SLC), including system L-type and A-type transporter.
the researchers cultured tumor cells using inhibitors from both transporters, and then CD8 T cells, and found that the system L transporter protein may be responsible for the tumor's consumption of methionine.
Then, the researchers compared SLC transcripts from CD8 T cells and tumor cells and found that SLC7A5 and SLC43A2 (two system L transporters) were expressed relatively high on tumor cells, while SLC43A2 was expressed very little in CD8 T cells, and only SLC7A5 was similar in effect CD8 T cells and some tumor cells.
if SLC43A2 is removed from tumor cells, tumor cell growth will be inhibited, suggesting that drug targeting SLC43A2 may promote anti-tumor immunity.
further analysis, the researchers determined that the high expression of SLC43A2 in tumors was associated with a decrease in T-cell immune response in cancer patients.
tumor SLC43A2 is associated with low T-cell immunity.
there are still many mechanism details that remain to be worked out, especially the detailed metabolic pathways of methionine," said Professor Weiping Z, senior author of the report and a professor at the University of Michigan's Roger Cancer Center.
we also need to understand how metabolic pathways may be different from tumor cells and T cells.
hope to find a target that is specific to tumor cells so that we don't hurt T cells, but affect tumors.
in summary, this study shows that long-standing crosstalk between the metabolism, histogenic patterns, and functional characteristics of tumor-infused T cells competes for methionine through SLC43A2, thereby impairing T-cell function and tumor immunity in metabolic and metastases.
, researchers are working with drug discovery experts to identify a small molecular inhibitor that targets methionine in tumor cells.
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