Researchers have discovered an immune regulator that appears to dictate glioblastoma (GBM) progression by shutting down immune surveillance, indicating a potential new area of therapeutic investigation. Findings from the preclinical study were published in the journal, Nature Communications.
"Classical wisdom is that brain tumor progression is linked to oncogene activation and tumor suppressor gene inactivation; however genetic and epigenetic mutations are not the only cause of GBM progression," said the senior author. "Some immune regulators can do the same thing and are key regulators of cancer, especially in certain tissues and environmental contexts."
GBM, unlike melanoma and lung cancers, does not attract robust T cell immune responses, and, so far, immunotherapies have had little success against it. GBM is considered "immunologically cold" or unreactive likely due to tumor elaborated immune suppressive factors.
Findings from the study indicate FGL2 (fibrinogen-like protein 2), which is known for suppressing the immune system, is highly expressed in GBM. Investigators showed that inactivating or "knocking out" FGL2 from the tumor cells can eliminate tumor progression in mice with intact immune systems. Understanding this type of expression is key to discovering causes of GBM progression.
Researchers showed the FGL2 present in tumor cells controls a specialized group of dendritic cells which activates T cells. More specifically, FGL2 secreted from tumor cells prevents the differentiation of a special subpopulation of CD103 dendritic cells that are essential for triggering the activation of the tumor killing T cells. The study also showed these dendritic cells must find a way to the tumor microenvironment in the central nervous center (CNS) in order to activate the T cells.
"This study is important because it shows that the immune system must interact in the CNS and in the tumor to be effective. Previously, this interaction was only thought to be necessary in specialized immune organs such as the lymph nodes," said the senior author. "It also shows a new mechanism of immune suppression that hasn't been described before, and it further supports how important FGL2 is to this disease."
The team also analyzed human GBM from The Cancer Genome Atlas and found that lower levels of FGL2 protein expression coupled with high levels of GM-CSF or IFN, DC differentiation inducer or T cell activator, are associated with longer survival of GBM patients.
https://www.mdanderson.org/newsroom/md-anderson-glioblastoma-study-shows-fgl2-protein-may-be-an-effective-target.h00-159299889.html
https://www.nature.com/articles/s41467-018-08271-x
Tumor protein inactivates immune system in glioblastoma
- 1,950 views
- Added
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Brain's immune cells put the brakes on neurons
Read more
Reference atlas of small noncoding RNAs in mouse tissues
Read more
Gene expression altered by direction of forces acting on cell
Read more
Reducing lignin levels in plants using CRISPR
Read more
Both excitatory and inhibitory systems play a role in memory consol…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar