IMMU-01. CYTOTOXIC AND SUPPRESSIVE IMMUNE CELL TRAFFICKING TO PEDIATRIC BRAIN TUMORS: A BALANCING ACT

Nicole Lieberman, Kristen Haberthur, Amira Davis, Harrison Chinn, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Sarah Leary, Courtney Crane
2017 Neuro-Oncology  
Abstracts iv27 NEURO-ONCOLOGY • JUNE 2017 and CHI3L1. We observed a marked increase in the invasive capacity of pHGG and DIPG patient-derived cultures upon the addition of active CM in both transwell and three-dimensional (3D) in vitro invasion assays. Analysis of several candidate proteins identified via proteomic screens highlighted two secreted factors, GRP78 and CRTAC1, which alone were sufficient to increase pHGG invasion. Abrogation of this pro-infiltrative effect was seen upon
more » ... een upon immunodepletion of GRP78 from the CM. Conversely CRISPR knockout of the Nogo receptor (NgR), on which CRTAC1 acts as an exogenous antagonist, markedly increased in vitro DIPG cell invasion. Both CRTAC1 and GRP78 have been shown to modulate RhoA activity in putatively complimentary ways, and we observed a significant reduction in RhoA activation upon exposure to active CM. As Rho-ROCK signalling modulates actin reorganisation and cell motility, this highlights a novel means by which the neural microenvironment drives glioma progression and potentially identifies a new set of therapeutic targets to limit glioma spread.
doi:10.1093/neuonc/nox083.112 fatcat:qofy3buaqzbf7bwt2wghdhdboe