IDH-mutant gliomas harbor fewer regulatory T cells in humans and mice
Leland G. Richardson, Linda T. Nieman, Anat 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
Abstract
) 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.