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- Title
Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities.
- Authors
Johnson, Amanda L.; Laterra, John; Lopez-Bertoni, Hernando
- Abstract
Despite its growing use in cancer treatment, immunotherapy has been virtually ineffective in clinical trials for gliomas. The inherently cold tumor immune microenvironment (TIME) in gliomas, characterized by a high ratio of pro-tumor to anti-tumor immune cell infiltrates, acts as a seemingly insurmountable barrier to immunotherapy. Glioma stem cells (GSCs) within these tumors are key contributors to this cold TIME, often functioning indirectly through activation and recruitment of pro-tumor immune cell types. Furthermore, drivers of GSC plasticity and heterogeneity (e.g., reprogramming transcription factors, epigenetic modifications) are associated with induction of immunosuppressive cell states. Recent studies have identified GSC-intrinsic mechanisms, including functional mimicry of immune suppressive cell types, as key determinants of anti-tumor immune escape. In this review, we cover recent advancements in our understanding of GSC-intrinsic mechanisms that modulate GSC-TIME interactions and discuss cutting-edge techniques and bioinformatics platforms available to study immune modulation at high cellular resolution with exploration of both malignant (i.e., GSC) and non-malignant (i.e., immune) cell fractions. Finally, we provide insight into the therapeutic opportunities for targeting immunomodulatory GSC-intrinsic mechanisms to potentiate immunotherapy response in gliomas.
- Subjects
IMMUNOREGULATION; STEM cells; GLIOBLASTOMA multiforme; HETEROGENEITY; CANCER stem cells; BRAIN tumors
- Publication
Frontiers in Oncology, 2022, Vol 12, p01
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2022.995498