BIOM-31. TEMPOROSPATIAL PROTEIN PROFILING OF HUMAN GLIOBLASTOMAS REVEALS MOLECULAR MECHANISMS AND BIOMARKERS UNDERLYING RESPONSES TO IMMUNE CHECKPOINT INHIBITION

Abstract Glioblastoma responses to immune checkpoint inhibition (ICI) are rare, and the molecular mechanisms underlying ICI incompletely understood. Thus, serial glioblastoma samples valuable resources for identifying biomarkers or therapeutic targets increase efficacy of in patients with glioblastoma. We obtained paired from 7 who underwent sequential surgery, ICI, eventual salvage surgery recurrence. Patients were distinguished as responders (n=3) non-responders (n=4) based on (1) MRI evidence tumor stability/reduction over 6+ months after (2) pathologic predominant treatment effect at time ICI. FFPE sections each (n=14) stained using H&E IHC/IF macrophages/microglia (CD68) T cells (CD3) analyzed light fluorescence microscopy. Six regions-of-interest (ROIs) comprising viable selected neuropathologist sample (n=84 ROIs). ROIs quantitative spatial profiling 72 proteins Nanostring Digital Profiler platform. Glioblastomas responding enriched T-cell (CD3, CD4, CD8) activation markers (CD25) compared initial surgery. Markers MAPK signaling suppressed pre-ICI post-ICI responders. p-ERK was non-responders. Myeloid (CD68, CD163, CD11c) Principle components analysis revealed CD8, CD20, CD11c, CTLA4, CD68, CD45, CD56, CD127) accounted 62% variance among In conclusion, temporospatial protein human glioblastomas reveals inhibition. These data establish a foundation functional studies reprogram immunosuppressive microenvironment sensitize tumors