SDPS-30 ANALYSIS OF THE BRAIN TUMOR MATRISOME REVEALS CANCER ASSOCIATED FIBROBLASTS PREDICT POOR IMMUNOTHERAPY RESPONSE IN GLIOBLASTOMA PATIENTS

Abstract

Abstract Excessive deposition of extracellular matrix (ECM) is a hallmark of solid tumors; however, it remains poorly understood which cellular and molecular components contribute to the formation of ECM stroma in central nervous system (CNS) tumors. Here, we undertook a pan-CNS analysis of retrospective gene expression datasets to characterize inter- and intra-tumoral heterogeneity of ECM remodeling signatures. We found that glioblastoma can be divided into two ECM-based subtypes that are influenced by the presence of cells resembling cancer associated fibroblasts (CAFs) and are conserved across a number of CNS lesions. In glioblastoma, CAF-like cells are correlated with unfavorable response to immune checkpoint blockade and poor patient survival across a subset of CNS tumors. We show that CAF-like cells reside in the perivascular niche, activate chemoattractant signaling pathways to recruit tumor-associated macrophages, and promote glioma stem-like cell phenotype. Our analysis provides insights into mechanisms underlying immunotherapy resistance in glioblastoma and suggests that targeting CAF-like cells may provide an effective approach to improve patient survival in a subset of CNS tumors.