Modeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockade

Xiaoyan Lan, Dorota A. Kedziorek, Chengyan Chu, Anna Jablonska, Shen Li, Mihoko Kai, Yajie Liang, Miroslaw Janowski, Piotr Walczak

Research output: Contribution to journalArticlepeer-review

Abstract

Currently, human glioma tumors are mostly modeled in immunodeficient recipients; however, lack of interactions with adaptive immune system is a serious flaw, particularly in the era when immunotherapies dominate treatment strategies. Our group was the first to successfully establish the orthotopic transplantation of human glioblastoma (GBM) in immunocompetent mice by inducing immunological tolerance using a short-term, systemic costimulation blockade strategy (CTLA-4-Ig and MR1). In this study, we further validated the feasibility of this method by modeling pediatric diffuse intrinsic pontine glioma (DIPG) and two types of adult GBM (GBM1, GBM551), in mice with intact immune systems and immunodeficient mice. We found that all three glioma models were successfully established, with distinct difference in tumor growth patterns and morphologies, after orthotopic xenotransplantation in tolerance-induced immunocompetent mice. Long-lasting tolerance that is maintained for up to nearly 200 d in GBM551 confirmed the robustness of this model. Moreover, we found that tumors in immunocompetent mice displayed features more similar to the clinical pathophysiology found in glioma patients, characterized by inflammatory infiltration and strong neovascularization, as compared with tumors in immunodeficient mice. In summary, we have validated the robustness of the costimulatory blockade strategy for tumor modeling and successfully established three human glioma models including the pediatric DIPG whose preclinical study is particularly thwarted by the lack of proper animal models.

Original languageEnglish (US)
Article number1776577
JournalOncoImmunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Glioma
  • brain tumor
  • costimulation blockade
  • immunocompetent
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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