Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.
作者： Vassilis Genoud , Eliana Marinari , Sergey I Nikolaev , John C. Castle , Valesca Bukur
DOI: 10.1080/2162402X.2018.1501137
关键词: Major histocompatibility complex 、 Malignancy 、 Glioma 、 Immunotherapy 、 Immune checkpoint 、 Blockade 、 CD8 、 Glioblastoma 、 Medicine 、 Cancer research
摘要: Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data other cancers, and results from studies 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, factor reported as prognostic indicator of ICB response. Consistent observation, SB28 completely resistant to ICB, contrasting treatment sensitivity more highly mutated GL261. Moreover, shows features poorly immunogenic tumor, MHC-I expression modest CD8+ T-cell infiltration, suggesting that it may present similar challenges for immunotherapy GBM. Based these immune reactivity, represent treatment-resistant malignancy likely mirror responses many tumors. We therefore propose particularly suitable optimization immunotherapy.
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