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Researchers at the MD Anderson Cancer Center at the University of Texas have discovered an immune regulator that seems to dictate the progression of glioblastoma (GBM) by stopping immune surveillance, indicating a potential new area of therapeutic investigation.
The results of the preclinical study conducted by Shulin Li, Ph.D., professor of pediatrics, and Amy Heimberger, M.D., professor of neurosurgery, were published in the January 25 issue. Nature Communications.
"The clbadical wisdom is that the progression of the brain tumor is related to the activation of the oncogene and the inactivation of the tumor suppressor gene, however, genetic and epigenetic mutations are not the only cause of the progression of the GBM, "said Li." 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 cancer, does not attract a robust immune response from T cells and, to date, immunotherapies have had little success. GBM is considered "immunologically cold" or probably non-reactive because of tumor-induced immunosuppressive factors.
The results of the study indicate that FGL2 (fibrinogen-like protein 2), known to suppress the immune system, is strongly expressed in the GBM. The researchers showed that inactivation or suppression of FGL2 tumor cells can rule out tumor progression in mice with intact immune systems. Understanding this type of expression is essential to discover the causes of the progression of GBM.
The first author, Jun Yan, Ph.D., researcher, has shown that the FGL2 protein present in tumor cells controls a specialized group of dendritic cells that activates T cells. More specifically, the FGL2 protein secreted by tumor cells prevents differentiation of a particular subpopulation of CD103 dendritic cells essential for triggering killer T cell activation. The study also showed that these dendritic cells had to find a way to create a tumor microenvironment in the central nervous center (CNS) in order to activate T cells.
"This study is important because it shows that the immune system must interact in the central nervous system and in the tumor to be effective." Previously, this interaction was considered necessary only in specialized immune organs such as lymph nodes, "said Heimberger . "It also shows a new mechanism of immune suppression that has not been described yet, and this further confirms the importance of FGL2 for this disease."
The team also badyzed human GBM from The Cancer Genome Atlas and found that lower levels of FGL2 protein expression, badociated with high levels of GM-CSF or IFN, an inducer of dendritic cells or a T cell activator, were badociated with longer survival of GBM patients.
Li and Heimberger are actively working on therapeutic strategies to target FGL2.
This article has been republished from materials provided by the MD Anderson Cancer Center of the University of Texas. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Jun Yan, et al. FGL2 promotes tumor progression in the CNS by suppressing the differentiation of CD103 + dendritic cells. Nature Communications. volume 10, article number: 448 (2019) DOI: https://doi.org/10.1038/s41467-018-08271-x
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