Journal
TRENDS IN IMMUNOLOGY
Volume 38, Issue 2, Pages 104-115Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2016.11.005
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Funding
- Alberta Innovates - Health Solutions/Alberta Cancer Foundation
- Canadian Institutes of Health Research
- Canada Research Chair (Tier 1) program
- Alberta Innovates [201300720] Funding Source: researchfish
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Glioblastoma is an aggressive and incurable primary brain tumor. While the blockade of immune checkpoints leads to reversal of T cell exhaustion in many cancers, the efficacy of this therapy in glioblastoma requires further consideration of the brain microenvironment beyond T cell activity. Neural cells are crucially dependent on glucose for survival, and tumor cells rabidly consume glucose; the glucose-deprived microenvironment further elevates immune checkpoint molecules to benefit tumor growth and exacerbate T cell exhaustion. We review here how immune checkpoints drive exhaustion in T cells while favoring tumor metabolism, and discuss how glucose competition in the unique CNS milieu is an important consideration to improve the outcomes of immune checkpoint blockade in glioblastoma.
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