Literature DB >> 27493076

Advanced age negatively impacts survival in an experimental brain tumor model.

Erik Ladomersky1, Lijie Zhai1, Galina Gritsina1, Matthew Genet1, Kristen L Lauing1, Meijing Wu1, C David James2, Derek A Wainwright3.   

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.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Entities:  

Keywords:  Cancer immunity; Glioma; Immunosuppression; TDO; Treg; Tryptophan

Mesh:

Substances:

Year:  2016        PMID: 27493076      PMCID: PMC5006183          DOI: 10.1016/j.neulet.2016.08.002

Source DB:  PubMed          Journal:  Neurosci Lett        ISSN: 0304-3940            Impact factor:   3.046


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