Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting

Irene Appolloni, Francesco Alessandrini, Davide Ceresa, Daniela Marubbi, Eleonora Gambini, Daniele Reverberi, Fabrizio Loiacono, Paolo Malatesta

Research output: Contribution to journalArticle

Abstract

The mutual reshape of tumor and immune system cells during tumor progression is a widely accepted notion in different cancers including gliomas. The importance of this phenomenon in shaping glioma progression and the mechanisms governing it, however, are not fully elucidated. Taking advantage of a well-characterized in vivo glioma model we performed an analysis of glioma cells transcriptomes at different stages of progression and unveiled the reorganization of glioma-immune system interactions. Specifically, we show that the inability of low-grade glioma cells to orthotopically graft in syngeneic immunocompetent mice, positively correlates with the abundance of infiltrating lymphocytes in donor tumors and with a highly immunostimulatory transcriptional profile. Notably, during tumor progression glioma cells downregulate these genes and the immune infiltrate shifts towards a pro-tumorigenic phenotype. Challenging low-grade gliomas by grafting into immunodeficient hosts revealed the crucial role of the adaptive immune system in constraining glioma progression. Finally, we observed that although progression still takes place in immunodeficient mice, it is slower, likely due to a milder selection thus reinforcing the view of a pivotal role for the immune system in regulating glioma progression.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalCancer Letters
Volume442
DOIs
Publication statusPublished - Feb 1 2019

Keywords

  • Glioblastoma
  • Immunoediting
  • PDGF-B
  • Retroviral induced glioma model
  • Tumor progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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