title: T Cell Exhaustion in Glioblastoma: Intricacies of Immune Checkpoints.
abstract: 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.
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Mirzaei
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Susobhan
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address: vyong@ucalgary.ca.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy; D016922:Cellular Senescence; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005909:Glioblastoma / Q000276:immunology* / Q000628:therapy; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D061025:Costimulatory and Inhibitory T-Cell Receptors; D005947:Glucose