Nature Sub-Journal: Reactivate the "paralyzed" immune system and launch an attack on deadly brain cancer

Glioma is the most common primary central nervous system tumor.
Because it has no clear boundary with normal brain tissue, it is difficult to completely remove, so it is not very sensitive to radiotherapy and chemotherapy, and it is very easy to recur, and there is no effective response.
Program.

To solve this problem, scientists are trying to find innovative treatments that use the immune system to fight glioma through therapeutic vaccines or immunotherapy, so that cancer patients who have no cures can benefit as soon as possible.

Recently, researchers from research institutions such as the German Cancer Research Center (DKFZ), the University of Freiburg Medical Center, and the Mannheim Medical School of Heidelberg University have jointly published an article titled Tryptophan metabolism in the top academic journal Nature Cancer.
Drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas article.

This study found that glioma cells can reprogram and invade immune cells through a common mutation, thereby "paralyzing" the body's immune defense against tumors.

To this end, researchers have developed an innovative treatment to reactivate the "paralyzed" immune system against tumors, that is, to fight gliomas through therapeutic vaccines or immunotherapy.

https://doi.
org/10.
1038/s43018-021-00201-z Interestingly, gliomas are not entirely composed of cancer cells.
Up to 50% of tumor masses are derived from microglia and monocytes The composition of macrophages, here we collectively refer to them as glioma-associated myeloid cells (GAM).

However, although macrophages are often referred to as "cell scavengers", they are "weak-hearted" in the face of gliomas and are not their opponents at all.

To this end, researchers began to look for other breakthroughs to combat glioma.

And I have a keen interest in the detection of the mutated gene "isocitrate dehydrogenase (IDH)" in 70% of gliomas.

Researchers have discovered that isocitrate dehydrogenase (IDH) mutations can cause glioma cells to release tumorigenic (R)-2-hydroxyglutarate (R-2-HG), which inhibits the immune system and T cell activity.
The invading macrophages are reprogrammed, blocking the immune response of the tumor, and causing serious "immune paralysis", which can easily escape the pursuit of the human immune system.

The IDH mutation causes the glioma cells to release R-2-HG.
But what makes the glioma cells so rampant? To find out, the researchers deciphered the molecular mechanism by which R-2-HG reprograms macrophages.

The study found that it was the cancer-promoting metabolite R-2-HG that interfered with the amino acid metabolism of "cell scavenger" macrophages, and activated the central immune system regulatory molecule aryl hydrocarbon receptor (AHR), thereby causing macrophages to produce Immunosuppressive response.

The AHR signal weakens the function of macrophages in IDH mutant gliomas.
Therefore, in view of the negative core role of aryl hydrocarbon receptors, the researchers decided to terminate the function of this key molecule in order to activate the paralyzed immune system.

Researchers combined T cell activation immunotherapy with immune checkpoint blocking and small molecule AHR inhibitors in animal models and found that the therapy can effectively extend the lifespan of mice with IDH mutant tumors.

Anti-tumor immunity can be reversed through the pharmacological suppression of AHR.
Researchers from the German Cancer Research Center (DKFZ) said: "Our current research results show how to avoid the immunosuppressive environment in the brain and further improve the effectiveness of this vaccine.
In the
near future, we will further verify in an early clinical trial that a therapeutic vaccine against IDH-mutated diffuse glioma can effectively trigger the expected immune response to help fight this currently almost incurable disease more effectively .

"in the future, we expect to have more patients benefit from this therapy, completely changed the pattern of cancer treatment, giving them the hope of life.

End reference materials: [1]https://#Abs1[2]https://medicalxpress.
com/news/2021-05-paralyzed-immune-cells -reactivated-brain.
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