Following anti-Ccl5 treatment, TUNEL staining and Brn3a immunofluorescence revealed decreased retinal cell death and increased RGC numbers relative to IgG-treated controls.
The most common brain tumor in children with NF1, the optic glioma, is composed of both cancer cells and non-cancer cells. Among the non-cancer cells in these tumors are immune system-like cells called microglia, which produce important factors that are partly responsible for maintaining optic glioma growth. Until recently, the identity of these factors has remained elusive.
Using new RNA sequencing methods pioneered by Dr. Elaine Mardis and her colleagues at the McDonnell Genome Institute at Washington University, Dr. Anne Solga discovered that one particular growth factor, a chemokine called Ccl5, is a major driver of optic glioma growth in mice. Dr. Solga, along with other investigators in the laboratory of Dr. David Gutmann, found that Ccl5 is made by microglia in these tumors. Furthermore, she showed that the addition of Ccl5 to optic glioma-like cells causes them to grow faster.
To determine whether blocking Ccl5 activity in Nf1 mice could reduce optic glioma growth, she took advantage of an immunotherapy approach using neutralizing antibodies. Following treatment with Ccl5 blocking antibodies, the growth of the optic gliomas was reduced.
These exciting findings demonstrate that blocking growth factors made by non-cancer cells can indeed slow tumor growth, opening the door for future immunotherapies to treat optic gliomas and related brain tumors.
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Solga AC, Pong WW, Kim KY, Cimino PJ, Toonen JA, Walker J, Wylie T, Magrini V, Griffith M, Griffith OL, Ly A, Ellisman MH, Mardis ER, Gutmann DH. RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth. Neoplasia. 17(10):776-88, 2015.