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Review
. 2023 Aug 9;4(4):e341.
doi: 10.1002/mco2.341. eCollection 2023 Aug.

Cancer stem cells in brain tumors: From origin to clinical implications

Shuyun Lin  1 , Kaishu Li  1 , Ling Qi  1
Affiliations
Review

Cancer stem cells in brain tumors: From origin to clinical implications

Shuyun Lin et al. MedComm (2020). .

Abstract

Malignant brain tumors are highly heterogeneous tumors with a poor prognosis and a high morbidity and mortality rate in both children and adults. The cancer stem cell (CSC, also named tumor-initiating cell) model states that tumor growth is driven by a subset of CSCs. This model explains some of the clinical observations of brain tumors, including the almost unavoidable tumor recurrence after initial successful chemotherapy and/or radiotherapy and treatment resistance. Over the past two decades, strategies for the identification and characterization of brain CSCs have improved significantly, supporting the design of new diagnostic and therapeutic strategies for brain tumors. Relevant studies have unveiled novel characteristics of CSCs in the brain, including their heterogeneity and distinctive immunobiology, which have provided opportunities for new research directions and potential therapeutic approaches. In this review, we summarize the current knowledge of CSCs markers and stemness regulators in brain tumors. We also comprehensively describe the influence of the CSCs niche and tumor microenvironment on brain tumor stemness, including interactions between CSCs and the immune system, and discuss the potential application of CSCs in brain-based therapies for the treatment of brain tumors.

Keywords: brain tumors; cancer stem cells; cell of origin; clinical implications; immune system; stemness regulators; targeted therapies; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Cancer stemness‐related discoveries in brain tumor. Early studies identified various brain CSC markers.
FIGURE 2
FIGURE 2
Intracellular forces regulate the stemness of CSC. Key intrinsic regulators include (A) epigenetic regulators, (B) transcription regulators (C) metabolism regulators, (D) kinases, (E) secretory molecules, and (F) other regulators.
FIGURE 3
FIGURE 3
Tumor microenvironmental influences on CSCs. The tumor‐associated stroma has an important role in the regulation of cancer stemness in glioma. Regulation of CSCs by their niche occurs through cell–matrix interactions and cell–cell interactions. The most prominent players in glioma CSC–stroma interactions include hypoxia, acidosis and extracellular matrix (ECM) remodeling; cellular components include endothelial cells.
FIGURE 4
FIGURE 4
Associations between CSCs and immune cells. Reciprocal communication between CSCs and infiltrating immune cell populations in the tumor microenvironment is a key factor that simultaneously induces the formation of CSCs and reprograms the immune response, thereby facilitating immune evasion by the tumor. Biological factors known to influence interactions between brain CSCs and immune cells are shown. TAM, tumor‐associated macrophage; MDSC, myeloid‐derived suppressor cell; DC, dendritic cell; MC, mast cell; NK, natural killer; CTL, cytotoxic T lymphocyte; Treg, regulatory T cell; MHC‐I, major histocompatibility complex class I; APM, antigen‐processing machinery.
FIGURE 5
FIGURE 5
Proposed therapeutic approaches to target CSCs. Novel approaches to target CSCs, as well as various available CSC‐based therapies that have the potential to be translated for use in the clinical treatment of brain tumors are shown. These approaches include: (A) targeting CSC markers, (B) Targeting vascular niche of CSCs, (C) targeting intrinsic and extrinsic regulators of CSCs, (D) CSC‐directed therapies. CAR, chimeric antigen receptor; NPs, polymer‐micellar nanoparticles (consisting of poly(styrene‐b‐ethylene oxide) (PS‐b‐PEO) and poly(lactic‐co‐glycolic) acid (PLGA)); Dual‐LP‐TMZ, dual‐targeting immunoliposome encapsulating TMZ; DC, dendritic cell.
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