Researchers have highlighted four “programs” of genetic expression in brain tumors that could explain the resistance of gliomas to immunotherapy.
- Brain cancers often resist immunotherapy.
- Researchers have highlighted four “programs” of genetic expression that could explain this resistance.
- This discovery could help develop drugs making immunotherapy more effective.
If immunotherapy is effectively fighting against many cancers, treatment is often put in difficulty in the face of brain tumors such as glioma.
But a new study, published in the journal Natureshed light on the resistance to immunotherapy of many brain cancers.
Immunotherapy resistant glioma: 4 “programs” of genetic expression in question
During this research by the Broad Institute of MIT, Harvard and Dana-Farber Cancer Institute (DFCI), scientists analyzed nearly 200,000 immune cells, called myeloid cells. The latter from samples of gliomas, the type of primitive cancer of the most common and aggressive brain.
The analyzes have revealed four “programs” of genetic expression-that is to say sets of genes with coordinated activity-which inhibit the immune system or make it more active.
“In two cases, the immune system was inflammatory: it was activated and potentially tried to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressants. Which partially deactivated the immune system and hampered its ability to fight cancer ”explain the authors in a press release.
“This study provides us with the data we need to create myeloid targeting strategies to modulate these programs and make immunotherapy more effective for patients with brain tumors”adds Tyler Miller, co-first author of the study.
Dexamethasone and gliom: pay attention to myeloid cells
These advances led the team to look at dexamethasone, a steroid generally used to reduce the swelling of the brain when the patient develops the first symptoms of glioma and known to reduce the immune response.
So far, researchers thought that this immunosuppressive character was mainly due to the effects of drugs on T lymphocytes. But the new study shows that treatment impacts myeloid cells: patients who took it, have signs of one of the immunosuppressive programs. During tests on laboratory cells, it was highlighted that the myeloid cells in contact with dexamethasone, continued to express the immunosuppressive programs long after stopping treatment.
“This suggests that the steroid could affect the response to immunotherapy even if it was administered to patients only for a short period”, Add the researchers. Faced with these elements, scientists propose that dexamethasone is prescribed with more sparing “To improve the efficiency of immunotherapy.”
“We hope this will encourage additional studies to identify ways to fight edema [gonflement du cerveau] Using different drugs and also to think about how we design clinical trials according to these results “, Indicates Tyler Miller.
In addition, he assures that it will be possible one day of “Manipulate the four programs with drugs to make immunotherapy more effective”.
