Single-Cell Omics in Dissecting Immune Microenvironment of Malignant Gliomas—Challenges and Perspectives

Abstract

Single-cell technologies allow precise identification of tumor composition at the single‑cell level, providing high-resolution insights into the intratumoral heterogeneity and transcriptional activity of cells in the tumor microenvironment (TME) that previous approaches failed to capture. Malignant gliomas, the most common primary brain tumors in adults, are genetically heterogeneous and their TME consists of various stromal and immune cells playing an important role in tumor progression and responses to therapies. Previous gene expression or immunocytochemical studies of immune cells infiltrating TME of malignant gliomas failed to dissect their functional phenotypes. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) are powerful techniques allowing quantification of whole transcriptomes or >30 protein targets in individual cells. Both methods provide unprecedented resolution of TME. We summarize the findings from these studies and the current state of knowledge of a functional diversity of immune infiltrates in malignant gliomas with different genetic alterations. A precise definition of functional phenotypes of myeloid and lymphoid cells might be essential for designing effective immunotherapies. Single-cell omics studies have identified crucial cell subpopulations and signaling pathways that promote tumor progression, influence patient survival or make tumors vulnerable to immunotherapy. We anticipate that the widespread usage of single-cell omics would allow rational design of oncoimmunotherapeutics.

Myeloid Cell Classification and Therapeutic Opportunities Within the Glioblastoma Tumor Microenvironment in the Single Cell-Omics Era

“…These results were consistent with the analytical techniques used, with flow cytometry revealing co-expression of immune costimulatory marker CD86 and the immunosuppressive marker CD206. The findings of macrophage co-expression of heterogeneous pro- and anti-tumor markers are corroborated by the results in a number of other studies ( 37 – 39 ). It is worth mentioning here that the expression of such markers can rapidly change in association with treatment, as indicated by the results of studies in which GBM patients received co-treatment with rapamycin and hydroxychloroquine or concurrent stereotactic radiotherapy with immune checkpoint blockade via programmed cell death protein 1 (PD-1) signal disruption ( 40 , 41 ).…”

Transcriptional landscape of human microglia implicates age, sex, and APOE‐related immunometabolic pathway perturbations

“…Activated microglia are a hallmark in both brain cancers and temporal lobe epilepsy in response to the inflammation (Darmanis et al, 2017 ; Kaminska et al, 2021 ; Kinoshita & Koyama, 2021 ; Morin‐Brureau et al, 2018 ; Ochocka et al, 2021 ). We acknowledge that the tissue used in this study is sourced from tumor or epileptogenic tissue adjacent regions in individuals with diagnoses of brain tumors or epilepsy, meaning it is not entirely healthy.…”

A roadmap for translational cancer glycoimmunology at single cell resolution

“…The spotlight is currently on the tremendous potential brought by multicomponent 3D models for personalised oncoimmunology. These approaches supported by multi-omics characterization at single cell resolution [ 309 , 310 ] are positively contributing to better understand the role played by the cancer microenvironment in disease [ 311 , 312 ]. The exploitation of bioinformatics and computational tools backed by artificial intelligence has been decisive towards this objective, setting a roadmap ready to be translated to cancer glycobiology.…”