Qiyuan Zhuang1 · Hui Yang1,2,3,4,5 · Ying Mao1,2,3,5,61 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
2 National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, China
3 Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China
4 Institute for Translational Brain Research, Fudan University, Shanghai 200032, China
5 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute for Translational Brain Research, Institutes of Brain Science, Fudan University, Shanghai 200032, China
6 Neurosurgical Institute of Fudan University, Shanghai 200032, China
Abstract
Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.
Keywords
Glioma origin; Stem/progenitor cell; Oncometabolite; Immune heterogeneity; Neuron-tumor interaction
