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This article is original by Translational Medicine Network.
Please indicate the source for reprinting.
Author: Catalina Introduction: Glioma is the most common primary central nervous system tumor.
Recently, scientists have discovered a reactivation of the "paralyzed" immune system Innovative therapies to combat malignant tumors.
With the development of biology and medicine, many diseases that have left people at a loss in the past are gradually alleviated and cured.
.
.
However, cancer as the "king of diseases" has not been completely defeated by humans.
Glioma, as the name suggests, is a central nervous system tumor that develops from the deterioration of glial cells, and is the most common primary central nervous system tumor.
Glioma is usually incurable.
It spreads in the brain and is difficult to remove completely with surgery.
Chemotherapy and radiotherapy usually only achieve limited results.
Therefore, oncologists are eagerly trying to find innovative treatments that use the immune system to combat gliomas, such as therapeutic vaccines or immunotherapy.
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 collaborated to publish an article in Nature Cancer entitled “Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas".
They found that glioma cells can reprogram and invade immune cells through a common mutation, thereby "paralyzing" the body's immune defense against the brain.
To this end, researchers have developed an innovative therapy that reactivates the "paralyzed" immune system to fight tumors and prolongs the lives of mice with IDH mutant tumors.
Interestingly, gliomas are not entirely composed of cancer cells: up to 50% of the tumor mass is composed of microglioma cells (the brain’s own phagocytic cells) and macrophages that enter the tumor through blood vessels.
However, although macrophages are "scavenger cells", they are too weak in front of glioma cells, so they can't compete.
So, when glioma comes, where does our immune system go? "If we are to make progress in developing immunotherapies or therapeutic vaccines, we need to understand exactly the behavior of the immune environment in the development of tumors.
In addition, we are concerned about whether the special genetic characteristics of glioma affect glioma-related immune cells.
I am very interested in functions that have special effects," explained a researcher from the German Cancer Research Center.
To this end, they specifically studied the RNA and protein profiles of individual microglia and macrophages.
Using mouse tumor models, they demonstrated the development of the immune environment during the disease process.
The integrated single-cell map identified different myeloid cell subpopulations in HGG.
Next, the researchers studied the mutated gene "isocitrate dehydrogenase (IDH)" that can be detected in 70% of gliomas.
They found that IDH mutations can cause glioma cells to release tumorigenic (R)-2-hydroxyglutarate (R-2-HG), which inhibits the immune system and T cell activity, allowing invading macrophages to be reprogrammed , Blocking the immune response of the tumor, causing serious "immune paralysis", thus easily escaping the pursuit of the human immune system.
AHR signal disrupts the function of macrophages in idh mutant gliomas.
So, why are gliomas always out of control? To solve this problem, the researchers deciphered the molecular mechanism of (R)-2-HG reprogramming macrophages.
They found that R-2-HG, a cancer-promoting metabolite, interferes with the amino acid metabolism of clear cells, thereby activating a central immune system regulatory molecule-aryl hydrocarbon receptor (AHR), and finally causing macrophages to produce an immunosuppressive response.
In view of the core role of the aryl hydrocarbon receptor, the researchers decided to specifically inactivate the function of this key molecule.
They combined immune checkpoint-blocking T cell activation immunotherapy with aryl hydrocarbon receptors and found that this therapy is effective in animal models and prolongs the lives of mice with IDH mutant tumors.
The anti-tumor immunity suppressed by IDH-mutated macrophages can be reversed by the suppression of AHR.
The author said: “Recently, we have demonstrated in an early clinical study that a therapeutic vaccine against IDH-mutated diffuse glioma can be Trigger the expected immune response in the research subjects.
"In short, glioma is one of the most difficult cancers in China's cancer campaign.
The road is long and I will look up and down.
I hope that scientists will continue to work hard to obtain clinical verification and eventually break the cancer barrier.
Reference materials: https:// Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options.
If you need health guidance, please go to a regular hospital.
Please indicate the source for reprinting.
Author: Catalina Introduction: Glioma is the most common primary central nervous system tumor.
Recently, scientists have discovered a reactivation of the "paralyzed" immune system Innovative therapies to combat malignant tumors.
With the development of biology and medicine, many diseases that have left people at a loss in the past are gradually alleviated and cured.
.
.
However, cancer as the "king of diseases" has not been completely defeated by humans.
Glioma, as the name suggests, is a central nervous system tumor that develops from the deterioration of glial cells, and is the most common primary central nervous system tumor.
Glioma is usually incurable.
It spreads in the brain and is difficult to remove completely with surgery.
Chemotherapy and radiotherapy usually only achieve limited results.
Therefore, oncologists are eagerly trying to find innovative treatments that use the immune system to combat gliomas, such as therapeutic vaccines or immunotherapy.
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 collaborated to publish an article in Nature Cancer entitled “Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas".
They found that glioma cells can reprogram and invade immune cells through a common mutation, thereby "paralyzing" the body's immune defense against the brain.
To this end, researchers have developed an innovative therapy that reactivates the "paralyzed" immune system to fight tumors and prolongs the lives of mice with IDH mutant tumors.
Interestingly, gliomas are not entirely composed of cancer cells: up to 50% of the tumor mass is composed of microglioma cells (the brain’s own phagocytic cells) and macrophages that enter the tumor through blood vessels.
However, although macrophages are "scavenger cells", they are too weak in front of glioma cells, so they can't compete.
So, when glioma comes, where does our immune system go? "If we are to make progress in developing immunotherapies or therapeutic vaccines, we need to understand exactly the behavior of the immune environment in the development of tumors.
In addition, we are concerned about whether the special genetic characteristics of glioma affect glioma-related immune cells.
I am very interested in functions that have special effects," explained a researcher from the German Cancer Research Center.
To this end, they specifically studied the RNA and protein profiles of individual microglia and macrophages.
Using mouse tumor models, they demonstrated the development of the immune environment during the disease process.
The integrated single-cell map identified different myeloid cell subpopulations in HGG.
Next, the researchers studied the mutated gene "isocitrate dehydrogenase (IDH)" that can be detected in 70% of gliomas.
They found that IDH mutations can cause glioma cells to release tumorigenic (R)-2-hydroxyglutarate (R-2-HG), which inhibits the immune system and T cell activity, allowing invading macrophages to be reprogrammed , Blocking the immune response of the tumor, causing serious "immune paralysis", thus easily escaping the pursuit of the human immune system.
AHR signal disrupts the function of macrophages in idh mutant gliomas.
So, why are gliomas always out of control? To solve this problem, the researchers deciphered the molecular mechanism of (R)-2-HG reprogramming macrophages.
They found that R-2-HG, a cancer-promoting metabolite, interferes with the amino acid metabolism of clear cells, thereby activating a central immune system regulatory molecule-aryl hydrocarbon receptor (AHR), and finally causing macrophages to produce an immunosuppressive response.
In view of the core role of the aryl hydrocarbon receptor, the researchers decided to specifically inactivate the function of this key molecule.
They combined immune checkpoint-blocking T cell activation immunotherapy with aryl hydrocarbon receptors and found that this therapy is effective in animal models and prolongs the lives of mice with IDH mutant tumors.
The anti-tumor immunity suppressed by IDH-mutated macrophages can be reversed by the suppression of AHR.
The author said: “Recently, we have demonstrated in an early clinical study that a therapeutic vaccine against IDH-mutated diffuse glioma can be Trigger the expected immune response in the research subjects.
"In short, glioma is one of the most difficult cancers in China's cancer campaign.
The road is long and I will look up and down.
I hope that scientists will continue to work hard to obtain clinical verification and eventually break the cancer barrier.
Reference materials: https:// Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options.
If you need health guidance, please go to a regular hospital.
