Glioma is the most common type of primary CNS tumor, composed of cells that resemble normal glial cells. Recent genetic studies have provided insight into the inter-tumoral heterogeneity of gliomas, resulting in the updated 2021 WHO classification of gliomas. Thorough understanding of inter-tumoral heterogeneity has already improved the prognosis and treatment outcomes of some types of gliomas. Currently, the challenge for researchers is to study the intratumoral cell heterogeneity of newly defined glioma subtypes. Cancer stem cells (CSCs) present in gliomas and many other tumors are an example of intratumoral heterogeneity of great importance. In this review, we discuss the modern concept of glioma stem cells and recent single-cell sequencing-driven progress in the research of intratumoral glioma cell heterogeneity. The particular emphasis was placed on the recently revealed variations of the cell composition of the subtypes of the adult-type diffuse gliomas, including astrocytoma, oligodendroglioma and glioblastoma. The novel data explain the inconsistencies in earlier glioma stem cell research and also provide insight into the development of more effective targeted therapy and the cell-based immunotherapy of gliomas. Separate sections are devoted to the description of single-cell sequencing approach and its role in the development of cell-based immunotherapies for glioma.
Keywords: CAR-T cells; adult-type diffuse gliomas; astrocytoma; glioblastoma; glioma stem cells; high-throughput single-cell analysis; intratumoral heterogeneity; oligodendroglioma; single-cell omics; single-cell sequencing.