Single-cell profiling of peripheral and local immune compartments reveal unique genotype-independent prognostic immune signatures across IDH-stratified glioma.
Jonathan H Sussman, Anthony R Cillo, Sajeev Kohli, Carly Cardello, Jonathan Patterson, Ebrar Akca, Angelo Angione, David Moon, Katharine Krueger, Ali Ghamari, Emily Xu, Jessica Xu, Antonio C Tarbay, Alex Li, Bhargavi R Budihal, Xiaoran Zhang, Omar Elghawy, Wojciech K Panek, Prajwal Rajappa, Kai Tan, Dario A A Vignali, Tullia C Bruno, Nduka M Amankulor
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引用次数: 0
Abstract
Background: Solid tumor immune suppression requires cooperation of tumor cells, local immune cells, peripheral circulating immune cells, and evolution of immune cell trajectories between peripheral and local environments. This study addresses a significant knowledge gap by characterizing peripheral and local immune environments in IDH Mutant (IDH-Mut) and IDH wildtype (IDH-WT) gliomas and defines novel immunological states with prognostic relevance across the glioma landscape.
Methods: We analyzed local and peripheral immune phenotypes in a cohort of 18 (6 IDH-Mut and 12 IDH-WT) gliomas with distinct genetic characteristics using paired human tumor and peripheral blood mononuclear cells (PBMCs) with single-cell RNA-sequencing (scRNA-seq).
Results: Our analyses revealed unique intratumoral and peripheral immune cellular ontogenies, including naïve CD4+ T cell enrichment in the IDH-Mut peripheral immune compartment, monocyte enrichment in IDH-WT glioma PBMCs, and emergence of a unique population of GZMH+ CD8+ T cells preferentially in the IDH-Mut microenvironment. Additionally, we found upregulation of TNF-α signaling and inflammatory response pathways in IDH-Mut-glioma-associated peripheral lymphoid cells versus IDH-WT tumors and identified a novel population of microglia-like cells in the peripheral blood of glioma patients with complement-interfacing characteristics. Applying intratumoral transcriptomic deconvolution via The Cancer Genome Atlas revealed genotype-independent, prognostic immune signatures across the malignant glioma landscape.
Conclusions: This study reveals variable expression of immune phenotypes in adult gliomas stratified by IDH status and characterizes immune compartment and genotype-dependent differences in the immunologic glioma landscape. These genotype-dependent, tumor and circulating immune ontogenies should guide future diagnostic and immunotherapeutic considerations in malignant glioma.
期刊介绍：
Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field.
The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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