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.
To solve this problem, scientists are trying to find innovative treatments that use the immune system to fight gliomas 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 School of Medicine of Heidelberg University have jointly published an article titled Tryptophan me in the top academic journal "Nature Cancer".
tabolism 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
Interestingly, gliomas are not entirely composed of cancer cells.
Up to 50% of tumor masses are composed of microglia and monocyte-derived macrophages.
Here we collectively refer to them as glioma-related 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
But what makes 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
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
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