Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas

Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A. Miller, Yunlong Liu, R. Timothy Bentley, Mahua Dey

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing. Here, we characterize the immunologic landscape and gene expression profiles of spontaneous canine glioma and evaluate its potential for serving as such a translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing were used to evaluate immune cell presence and gene expression in healthy and glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T cells). The peripheral blood of glioma-bearing dogs also contained a relatively greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing animals also possessed a greater proportion of immune cells expressing the immune checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes in our canine populations revealed several genetic changes paralleling those known to occur in human disease. Naturally occurring canine glioma has many characteristics closely resembling human disease, particularly with respect to genetic dysregulation and host immune responses to tumors, supporting its use as a translational model in the preclinical testing of prospective anti-glioma therapies proven successful in murine studies.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Neuro-Oncology
DOIs
StateAccepted/In press - Jan 12 2018

Fingerprint

Oligodendroglioma
Transcriptome
Glioma
Canidae
RNA Sequence Analysis
Regulatory T-Lymphocytes
Brain Neoplasms
Dendritic Cells
In Situ Hybridization
Neoplasms
Animal Models
Dogs
RNA
T-Lymphocytes
Gene Expression

Keywords

  • Gene expression
  • Glioblastoma
  • Immunotherapy
  • Malignant glioma
  • Spontaneous canine glioma

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Filley, A., Henriquez, M., Bhowmik, T., Tewari, B. N., Rao, X., Wan, J., ... Dey, M. (Accepted/In press). Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas. Journal of Neuro-Oncology, 1-11. https://doi.org/10.1007/s11060-018-2753-4

Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas. / Filley, Anna; Henriquez, Mario; Bhowmik, Tanmoy; Tewari, Brij Nath; Rao, Xi; Wan, Jun; Miller, Margaret A.; Liu, Yunlong; Bentley, R. Timothy; Dey, Mahua.

In: Journal of Neuro-Oncology, 12.01.2018, p. 1-11.

Research output: Contribution to journalArticle

Filley, A, Henriquez, M, Bhowmik, T, Tewari, BN, Rao, X, Wan, J, Miller, MA, Liu, Y, Bentley, RT & Dey, M 2018, 'Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas', Journal of Neuro-Oncology, pp. 1-11. https://doi.org/10.1007/s11060-018-2753-4
Filley, Anna ; Henriquez, Mario ; Bhowmik, Tanmoy ; Tewari, Brij Nath ; Rao, Xi ; Wan, Jun ; Miller, Margaret A. ; Liu, Yunlong ; Bentley, R. Timothy ; Dey, Mahua. / Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas. In: Journal of Neuro-Oncology. 2018 ; pp. 1-11.
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