Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models. (2nd December 2018)

• Record Type: Journal Article
• Authors: Genoud, Vassilis; Marinari, Eliana; Nikolaev, Sergey I; Castle, John C.; Bukur, Valesca; Dietrich, Pierre-Yves; Okada, Hideho; Walker, Paul R.
• Is Part Of: Oncoimmunology. Volume 7:Number 12(2018)
• Publication Date: 2018-12-02
• Subjects: Immune checkpoint blockade -- Glioblastoma -- GL261 -- SB28 -- Mutational load; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1501137
• Languages: English
• ISSNs: 2162-402X

Abstract

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.