Immunotherapy has proven effective in treating a variety of cancers, but brain tumors remain stable. Now a new study suggests that slow-growing brain tumor that occurs in patients with neurofibromatosis type 1 (NF1), can be susceptible to immunotherapy, which gives a stimulus to the immune system to fight cancer.
The results, made by an international consortium led by researchers from the College of Physicians and Surgeons of Columbia University, was published today in the journal Nature Medicine.
Approximately 100 000 people in the United States have NF1, a hereditary disease that may lead to the development of tumors of the nervous system, including the type of brain tumor called glioma . Children usually have slow-growing type of glioma, while adults often have a more aggressive type.
But it is slow-growing or not, gliomas difficult to treat. Most of them are highly resistant to chemotherapy and radiation therapy may aggravate rather than alleviate symptoms such as headaches and convulsions. Since tumor usually cover sensitive areas of the brain surgery is rarely possible.
Immunotherapy has been successful for some patients with melanoma, lymphoma and several other types of cancer. But clinical trials have shown that as long as it is not effective for brain cancer in general.
A global study has revealed vulnerabilities in NF1 brain tumors
Surprisingly little was known about the molecular changes that occur in NF1 brain tumors, which hampers the development of targeted therapies. In this study, researchers from 25 institutions around the world, led by the Colombian doctor Antonio Iavarone and Anna Lasorelloy, carried out an in-depth analysis of tumor samples from 56 patients to create the first complete list of genetic, epigenetic and immune alterations in gliomas NF1.
"This list will give us a much better idea of how to develop individual therapies - Iavarone says - but the two results of our study may have direct clinical implications for patients with NF1».
Many slow-growing gliomas NF1 seem to be susceptible to immunotherapy.
Immunotherapy is not effective for the majority of brain tumors because tumor infiltrated a large number of cells, called macrophages, which prevent the attack of the immune system.
New research has shown that many of the slow-growing gliomas NF1 contain few macrophages and produce proteins called neoantigenami that can cause an attack of the immune system.
"We were surprised to find that about 50 percent slow-growing gliomas NF1 contain a large number of T-cells that can destroy cancer cells," - says Lasorella. These "vysokoimmunnye" tumors are good candidates for the treatment of immunotherapy, which can unleash the T cells, and is currently in clinical trials are planned.
This study also found that a subgroup of brain tumors in patients without NF1 has the same molecular profile as the slow-growing gliomas NF1. Future studies will have to determine whether these "NF1-like glioma" brain tumor the same immune properties and potentially susceptible to immunotherapy.
Aggressive glioma NF1 can be reduced using agents that damage DNA.
Despite the fact that aggressive tumor NF1 were filled macrophages and probably oppose immunotherapy, the researchers also found that many had a genetic defect which may make them more sensitive to treatment, damaging DNA.
The cells in these aggressive tumors can grow, but new cells contain a lot of DNA errors. "If we handle aggressive tumor DNA damaging agents, we can make even more mistakes in the DNA, which ultimately did not allow the cells to proliferate and stop tumor growth," - said Iavarone.
Radiation therapy and some modern cancer drugs damage DNA, but also the development of drugs that may be more effective in cancer cells with this particular genetic defect.