IDH-mutant gliomas harbor fewer regulatory T cells in humans and mice

• Main Authors: Leland G. Richardson, Linda T. Nieman, Anat O. Stemmer-Rachamimov, Xijin S. Zheng, Khalifa Stafford, Hiroaki Nagashima, Julie J. Miller, Juri Kiyokawa, David T. Ting, Hiroaki Wakimoto, Daniel P. Cahill, Bryan D. Choi, William T. Curry
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2020-01-01
• Series: OncoImmunology
• Subjects: regulatory t cells; idh-mutation; glioma; immune microenvironment
• Online Access: http://dx.doi.org/10.1080/2162402X.2020.1806662

The metabolic gene isocitrate dehydrogenase 1 (IDH1) is commonly mutated in lower grade glioma (LGG) and secondary glioblastoma (GBM). Regulatory T cells (Tregs) play a significant role in the suppression of antitumor immunity in human glioma. Given the importance of Tregs in the overall framework of designing immune-based therapies, a better understanding on their association with IDH mutational status remains of critical clinical importance. Using multispectral imaging analysis, we compared the incidence of Tregs in IDH-mutant and IDH wild-type glioma from patient tumor samples of LGG. An orthotopic IDH-mutant murine model was generated to evaluate the role of mutant IDH on Treg infiltration by immunohistochemistry. When compared to IDH wild-type controls, Tregs are disproportionally underrepresented in mutant disease, even when taken as a proportion of all infiltrating T cells. Our findings suggest that therapeutic agents targeting Tregs may be more appropriate in modulating the immune response to wild-type disease.