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

Oncoimmunology. 2018 Sep 5;7(12):e1501137. doi: 10.1080/2162402X.2018.1501137. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

Grant support

Funding was provided by the 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.).