IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma - Archive ouverte HAL Access content directly
Journal Articles Neuro-Oncology Year : 2023

IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma

Jérôme Archambeau
  • Function : Author
Elodie Lafont
Marc Aubry
Raphaël Pineau
Rachel Boniface
  • Function : Author
  • PersonId : 918824
Diana Pelizzari Raymundo
Efstathios-Iason Vlachavas
  • Function : Author
Matthieu Le Gallo
Pierre Jean Le Reste
  • Function : Author
  • PersonId : 1036741
Tanya Fainsod-Levi
  • Function : Author
Zvi Granot
  • Function : Author
Boaz Tirosh
  • Function : Author
Juhi Samal
  • Function : Author
Abhay Pandit
Annabelle Monnier
  • Function : Author
  • PersonId : 834355
Jean Mosser
  • Function : Author
  • PersonId : 835062
Aristotelis Chatziioannou
  • Function : Author
  • PersonId : 1014198
Véronique Quillien
Eric Chevet

Abstract

BACKGROUND: Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies on UPR to sustain growth. We recently showed that IRE1 alpha (referred to IRE1 hereafter), one of the UPR transducers, promotes GB invasion, angiogenesis and infiltration by macrophage. Hence, high tumor IRE1 activity in tumor cells predicts worse outcome. Herein, we characterized the IRE1-dependent signaling that shapes the immune microenvironment towards monocytes/macrophages and neutrophils. METHODS: We used human and mouse cellular models in which IRE1 was genetically or pharmacologically invalidated and which were tested in vivo. Publicly available datasets from GB patients were also analyzed to confirm our findings. RESULTS: We showed that IRE1 signaling, through both the transcription factor XBP1s and the regulated IRE1-dependent decay (RIDD) controls the expression of the ubiquitin-conjugating E2 enzyme UBE2D3. In turn, UBE2D3 activates the NFκB pathway, ensuing chemokine production and myeloid infiltration in tumors. CONCLUSION: Our work identifies a novel IRE1/UBE2D3 pro-inflammatory axis that plays an instrumental role in GB immune regulation.
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Year Month Jours
Avant la publication
Friday, June 28, 2024
Embargoed file
0 2 11
Year Month Jours
Avant la publication
Friday, June 28, 2024
Embargoed file
Friday, June 28, 2024
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Dates and versions

hal-04388457 , version 1 (29-02-2024)

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Joanna Obacz, Jérôme Archambeau, Elodie Lafont, Manon Nivet, Sophie Martin, et al.. IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma. Neuro-Oncology, 2023, Neuro-Oncology, ⟨10.1093/neuonc/noad256⟩. ⟨hal-04388457⟩
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