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In many characteristics of cancer cells, "eosinophils" is the direction that researchers are concerned about Cancer cells release a large amount of lactic acid , which can be used by themselves, such as participating in P53 protein suppression.At the same time, lactic acid can release a special barrier of immunosuppressive suppression in the tumor microe environment.
Under normal circumstances, T cells have been exhausted under uninterrupted tumor antigen stimulation. Some T cells have gradually transformed into a state of ending differentiation. Their self -update ability and effect molecular molecules The release ability is significantly weakened, and the acid released by cancer cells is likely to give them the last blow.
Recently, the research team of the University of Pittsburgh published a paper in "Nature-Immunology". They found that When T cells are in a acidic tumor microenvidic environment, they will be forced to use lactic acid Absorb the energy metabolism of the cells in the cell, further damage the energy metabolism of the cells, and reduce the intracellular nutrition level. The analysis of T cells shows that the more T -cells move towards the failure, the more likely it is to absorb more lactic acid, which also accelerates the death of T cells .
In addition, the researchers also found a new highlight, When they block the lactic acid absorption of T-cells, they block These cells began to gradually restore activity and re -control the growth of tumors .Professor Greg Delgoffe of the research communications pointed out that generally everyone will think that T cells with end -differential failure are useless, but new studies have proved that they are still useful, and the secret is to prevent them from absorb lactic acid.
Although everyone already knows that cancer cells secrete lactic acid, whether T cells can absorb lactate still depend on its own "will".Therefore, the research team pays special attention to the metabolic product transfer protein on the surface of the T cells. Only when the molecular activity participating in lactic acid transportation among these proteins is highly active can the cells actively exchange lactic acid with the surrounding environment.
Picture Source: 123rf
In the analysis, soluble carrier (SLC) The protein family has attracted special attention.Because cancer cells themselves like to express SLC, which allows them to better transfer nutrients into the cells from the outside and output lactic acid to the outside of the cell.And what is the SLC state of T cells?
With this problem, the research team has built a batch of melanoma mice and received tumor samples after a period of time. cell.The analysis results show that most SLCs on the surface of these cells are very low, which indicates that T cells are far weaker than cancer cells in terms of nutritional competition.
However, there are very few SLC family members on the failure T cells, which has a high expression, the most significant of which is monocular carboxylic acid transshipment 11 (MCT11) This protein is very important for lactic acid transportation.This means that Fast T cells are not able to fight for cancer cells, but the ability to obtain lactic acid is better, which also doubles the survival of T cells.
▲ The MCT11 of the failure T cells accelerate the absorption of lactic acid ( Picture source: Reference Data [1]
Researchers try to knock on tumors except tumor The mices MCT11 gene may use the MCT11 antibody to block its function. Both methods can inhibit the lactic acid transportation process of T cells in tumor failure. Tumor mice for MCT11 antibody treatment, their tumor progress is obviously controlled, especially when combined with PD-1 inhibitors, can more effectively remove tumor .
At present, the research team is promoting MCT11 antibody -related research, especially to determine whether it has a similar effect in human failure T cells.The author pointed out that MCT11 is almost expressed in the failure T cells, and these cells often appear inside the tumor, which means that the MCT11 inhibitor will have a high degree of targetedness and will not damage healthy cells and tissues. Cancer therapy target.
Reference Data:
[1] PERALTA, R.M., XIE, B., Lontos, K. Et Al. DysFunction of Exhausted T Cells is ENFORCED BY MCT11-Mediated Lactate Metabolism. Nat Immunol (2024). Ming Kangde The content WeChat team, welcome to the circle of friends and refer to other platforms.If there is a need to open a whitelist, please reply to "Reprinted" to get the reprinting notice on the "Academic Jingwei" public account homepage.For other cooperation needs, please contact [email protected].
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