TY - JOUR
T1 - Exploring glioblastoma stem cell heterogeneity
T2 - Immune microenvironment modulation and therapeutic opportunities
AU - Johnson, Amanda L.
AU - Laterra, John
AU - Lopez-Bertoni, Hernando
N1 - Funding Information:
This study is funded by the National Institute of Neurological Disorders and Stroke (NINDS) grants 1R01NS110087, 1R01NS096754 (JL), 1R01NS120949 (HLB).
Publisher Copyright:
Copyright © 2022 Johnson, Laterra and Lopez-Bertoni.
PY - 2022/9/21
Y1 - 2022/9/21
N2 - 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.
AB - 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.
KW - cancer stem cell
KW - cancer therapy
KW - cellular mimicry
KW - immunomodulation
KW - multi omics
KW - single-cell sequencing
KW - spatial analysis
UR - http://www.scopus.com/inward/record.url?scp=85140634852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140634852&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.995498
DO - 10.3389/fonc.2022.995498
M3 - Review article
C2 - 36212415
AN - SCOPUS:85140634852
SN - 2234-943X
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 995498
ER -