FGL2 protein may be an effective target for glioblastoma


Researchers at the University of Texas MD Anderson Cancer Center have discovered an immune regulator that appears to dictate the progression of glioblastoma (GBM) by closing immunological surveillance, indicating a potential new area for therapeutic research.

The results of the preclinical study led by Shulin Li, Ph.D., professor of pediatrics, and Amy Heimberger, MD, professor of neurosurgery, were published in the online edition of January 25. Communications of nature.

"The classic wisdom is that brain tumor progression is linked to oncogene activation and inactivation of the tumor suppressor gene, however, genetic and epigenetic mutations are not the only cause of GBM progression," Li said. Immune regulators can do the same thing and are the main 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 to be "immunologically cold" or non-reactive, probably due to immunosuppressive factors made by tumor.

Findings from the study indicate that FGL2 (fibrinogen-like protein 2), which is known to suppress the immune system, is highly expressed in GBM. Researchers have shown that inactivation or "knock-out" of FGL2 from tumor cells can eliminate tumor progression in mice with intact immune systems. Understanding this type of expression is critical to discovering the causes of GBM progression.

The first author Jun Yan, Ph.D., a research scientist, has shown that FGL2 present in tumor cells controls a specialized group of dendritic cells that activate T cells. More specifically, FGL2 secreted from tumor cells prevents the differentiation of a special subpopulation of CD103 dendritic cells which are essential for triggering the activation of T cells that kill tumors. The study also showed that these dendritic cells must find a way to the tumor microenvironment in the central nervous system (CNS) in order to activate 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 believed to be necessary in specialized immune organs such as lymph nodes, "said Heimberger. "It also shows a new mechanism of immunosuppression that has not been described before, and even supports how important FGL2 is for this disease."

The team also looked at the human GBM of the Cancer Genome Atlas and found that lower levels of FGL2 protein expression combined with high levels of GM-CSF or IFN, inducing differentiation of DC or T-cell activator, are associated with higher survival of patients with GBM.

Li and Heimberger are actively working on therapeutic strategies to achieve FGL2.

This article has been republished from materials provided by the University of Texas MD Anderson Cancer Center. Note: Material may have been edited for length and content. For more information, please contact the cited source.

Reference: Jun Yan, et al. FGL2 promotes tumor progression in the CNS, suppressing the differentiation of CD103 + dendritic cells. Communications of nature. volume 10, number of article: 448 (2019) DOI: https://doi.org/10.1038/s41467-018-08271-x


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