In Silico Analysis of Changes in Immunological Landscape During Malignant Transformation of IDH-mutant Low-grade Gliomas. (16th November 2020)

• Record Type: Journal Article
• Authors: Yeung, Jacky; Vesely, Matthew; Antonios, Joseph P; Miyagishima, Danielle F
• Is Part Of: Neurosurgery. Volume 67(2010)Supplement 1
• Publication Date: 2020-11-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa447_835
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Immunotherapy is one of the most promising current cancer treatment strategies. However, the effective use of immunotherapy for IDH-mutant low-grade gliomas (LGGs) is hindered by the lack of understanding of their immunological landscape. METHODS: We utilized CIBERSORTx to deconvolute the relative fractions of 22 immune cell subsets in 28 paired-samples of low- and high-grade gliomas. We analyzed changes in each immune cell subset before and after malignant transformation. We compared the inferred infer immune cell type-specific gene expression profiles using class comparison. We used Metascape to analyze the enriched pathways. Progression-free survival (PFS) was compared using changes in the relative fractions of each immune cell type. RESULTS: The predominant immune subset in LGG is M2 macrophages, followed by activated mast cells and monocytes. We found that the predominant immune subset in lower grade gliomas (LGG) is M2 macrophages, followed by activated mast cells and monocytes. In addition, CD4+ T cells outnumber CD8+ T cells within the tumor microenvironment (TME) of LGGs.As gliomas became more malignant, there were fewer activated natural killer (NK) cells ( P = .07), activated mast cells ( P = .0001), and monocytes ( P = .049). Most striking is the accumulation of M2 macrophages in the higher grade gliomas when compared to preexisting lower grade samples ( P < .0001). Immune-related genes were differentially expressed in monocytes/macrophages after malignant transformation. Significant increase in PFS is observed in patients that had an increase in activated NK cells or plasma cells. CONCLUSION: This study demonstrates patient-specific changes in immune cell subsets that occur during malignant transformation of IDH-mutant low-grade gliomas. Our findings have implications in optimizing immunotherapeutic strategies for these tumors.