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Scientific article
English

Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models

Published inOncoImmunology, vol. 7, no. 12, e1501137
Publication date2018
Abstract

Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261. Moreover, SB28 shows features of a poorly immunogenic tumor, with low MHC-I expression and modest CD8+ T-cell infiltration, suggesting that it may present similar challenges for immunotherapy as human GBM. Based on these key features for immune reactivity, SB28 may represent a treatment-resistant malignancy likely to mirror responses of many human tumors. We therefore propose that SB28 is a particularly suitable model for optimization of GBM immunotherapy.

Keywords
  • GL261
  • Glioblastoma
  • Immune checkpoint blockade
  • Mutational load
  • SB28
Funding
  • Autre - Nuovo Soldati foundation for cancer research (V.G.), National Institute of Neurological Disorders and Stroke/National Institutes of Health (R35 NS105068) (H.O.), the Fondation Privée des HUG (P.W.) and the Association Frédéric Fellay (P.W. and P.Y.D.)
Citation (ISO format)
GENOUD, Vassilis et al. Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models. In: OncoImmunology, 2018, vol. 7, n° 12, p. e1501137. doi: 10.1080/2162402X.2018.1501137
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Article (Published version)
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Identifiers
ISSN of the journal2162-4011
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