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REVIEW
Year : 2022  |  Volume : 5  |  Issue : 2  |  Page : 56-61

Overcoming T-cell exhaustion in glioblastoma: A narrative review


1 Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
2 Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; Department of Pathology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Il, USA

Correspondence Address:
Mr. Xisen Wang
Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_16_22

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Immunotherapy is typically ineffective against glioblastoma (GBM) due to inherent and adaptive resistance. Initial immunotherapy results for GBM have been disappointing. In this regard, T-cell exhaustion is a major barrier to successful treatment. The recognition of exhausted CD8+ T cell (Tex) pedigree is currently undergoing a paradigm shift. This review introduces major findings in this field to provide an up-to-date perspective on epigenetic, transcriptional, metabolic, and spatial heterogeneity, as well as interactions with tumor microenvironment cells of anti-tumoral CD8+ Tex from the following aspects: (i) Epigenetic and transcriptional mechanisms underlying T-cell exhaustion, (ii) Metabolic factors underpinning T-cell exhaustion, (iii) Contribution of multiple cell types to T-cell exhaustion, (iv) Occurrence of T-cell exhaustion at multiple locations, and (v) T-cell exhaustion may not always be terminal. These novel insights afford a wide range of new therapeutic approaches to overcome T-cell exhaustion in GBM.


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