Regulatory T cells are not a strong predictor of survival for patients with glioblastoma

BACKGROUND: Regulatory T cells (Tregs) are potentially prognostic indicators in patients with glioblastoma. If differences in frequency of Tregs in tumor or blood account for substantial variation in patient survival, then reliably measuring Tregs may enhance treatment selection and improve outcomes. METHODS: We measured Tregs and CD3+ T cells in tumors and blood from 25 patients with newly diagnosed glioblastoma. Tumor-infiltrating Tregs and CD3+ T cells, measured by quantitative DNA demethylation analysis (epigenetic qPCR) and by immunohistochemistry, and peripheral blood Treg proportions measured by flow cytometry were correlated with patient survival. Additionally, we analyzed data from The Cancer Genome Atlas (TCGA) to correlate the expression of Treg markers with patient survival and glioblastoma subtypes. RESULTS: Tregs, as measured in tumor tissue and peripheral blood, did not correlate with patient survival. Although there was a correlation between tumor-infiltrating Tregs expression by epigenetic qPCR and immunohistochemistry, epigenetic qPCR was more sensitive and specific. Using data from TCGA, mRNA expression of Forkhead box protein 3 (FoxP3) and Helios and FoxP3 methylation level did not predict survival. While the classical glioblastoma subtype corresponded to lower expression of Treg markers, these markers did not predict survival in any of the glioblastoma subtypes. CONCLUSIONS: Although immunosuppression is a hallmark of glioblastoma, Tregs as measured in tissue by gene expression, immunohistochemistry, or demethylation and Tregs in peripheral blood measured by flow cytometry do not predict survival of patients. Quantitative DNA demethylation analysis provides an objective, sensitive, and specific way of identifying Tregs and CD3+ T cells in glioblastoma.

Thomas, Alissa A.
Fisher, Jan L.
Rahme, Gilbert J.
Hampton, Thomas H.
Baron, Udo
Olek, Sven
Schwachula, Tim
Rhodes, C. Harker
Gui, Jiang
Tafe, Laura J.
Tsongalis, Gregory J.
Lefferts, Joel A.
Wishart, Heather
Kleen, Jonathan
Miller, Michael
Whipple, Chery A.
de Abreu, Francine B.
Ernstoff, Marc S.
Fadul, Camilo E.
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PMID: 25618892 PMCID: PMC4483125

Turabian/Chicago Citation

Alissa A. Thomas, Jan L. Fisher, Gilbert J. Rahme, Thomas H. Hampton, Udo Baron, Sven Olek, Tim Schwachula, C. Harker Rhodes, Jiang Gui, Laura J. Tafe, Gregory J. Tsongalis, Joel A. Lefferts, Heather Wishart, Jonathan Kleen, Michael Miller, Chery A. Whipple, Francine B. de Abreu, Marc S. Ernstoff and Camilo E. Fadul. 2015-06. "Regulatory T cells are not a strong predictor of survival for patients with glioblastoma." Neuro-Oncology 17: 6: 801-809. 10.1093/neuonc/nou363.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/neuonc/nou363 | issn = 1523-5866 | volume = 17 | pages = 801-809 | last = Thomas | first = Alissa A. | coauthors = Fisher, Jan L., Rahme, Gilbert J., Hampton, Thomas H., Baron, Udo, Olek, Sven, Schwachula, Tim, Rhodes, C. Harker, Gui, Jiang, Tafe, Laura J., Tsongalis, Gregory J., Lefferts, Joel A., Wishart, Heather, Kleen, Jonathan, Miller, Michael, Whipple, Chery A., de Abreu, Francine B., Ernstoff, Marc S., Fadul, Camilo E. | title = Regulatory T cells are not a strong predictor of survival for patients with glioblastoma | journal = Neuro-Oncology | date = 2015-06 | pmid = | pmc = }} </ref>