title: Advanced age negatively impacts survival in an experimental brain tumor model.
abstract: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future.
authors: Department of Neurological Surgery, USA.
authors: Erik
authors: E
authors: Ladomersky
authors: Department of Neurological Surgery, USA.
authors: Lijie
authors: L
authors: Zhai
authors: Department of Neurological Surgery, USA.
authors: Galina
authors: G
authors: Gritsina
authors: Department of Neurological Surgery, USA.
authors: Matthew
authors: M
authors: Genet
authors: Department of Neurological Surgery, USA.
authors: Kristen L
authors: KL
authors: Lauing
authors: Department of Neurological Surgery, USA.
authors: Meijing
authors: M
authors: Wu
authors: Department of Neurological Surgery, USA; Department of Biochemistry and Molecular Genetics, USA; Northwestern Brain Tumor Institute,USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
authors: C David
authors: CD
authors: James
authors: Department of Neurological Surgery, USA; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Northwestern Brain Tumor Institute,USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. Electronic address: Derekwainwright@northwestern.edu.
authors: Derek A
authors: DA
authors: Wainwright
mesh_terms: D000375:Aging; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000378:metabolism / Q000503:physiopathology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014364:Tryptophan / Q000378:metabolism
chemical_list: C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan
keywords: Cancer immunity; Glioma; Immunosuppression; TDO; Treg; Tryptophan