Children with NF1 are prone to develop brain tumors, specifically gliomas affecting the optic nerve and brainstem. These tumors are typically slow growing, and usually cannot be surgically removed. For this reason, most treatments involve the use of agents (chemotherapy) that slow the growth of the tumor cells. While these therapies have been effective in some children with NF1-associated gliomas, there remains a pressing need to develop alternative treatments.
Previous studies from the laboratory of NF Center Director Dr. David H. Gutmann have shown that immune system cells, called microglia, are abundant in both human and mouse NF1-associated brain tumors, and that blocking their function in Nf1 mouse models of optic glioma reduces tumor growth. However, it was not clear how these microglia become activated to support tumor formation and growth.
In a new study, led by postdoctoral fellows, Yuan Pan, PhD and Min Xiong, MD, PhD, they now show that microglia can be programmed to support tumor formation and growth by T cells. T cells are important immune system cells found in the blood, which recently have emerged as exciting new targets for cancer therapy.
Drs. Pan and Xiong discovered that T cells produce signals that act on microglia to allow them to secrete growth factors that facilitate tumor growth. The findings that T cells instruct microglia to support NF1 glioma growth suggests new therapies that block T cell function.
This report was published in the journal Genes and Development.
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Pan Y, Xiong M, Chen R, Ma Y, Corman C, Maricos M, Kindler U, Semtner M, Chen YH, Dahiya S, Gutmann DH. Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth. Genes Dev. 2018 Apr 1;32(7-8):491-496. doi: 10.1101/gad.310797.117. Epub 2018 Apr 9.