文章基本信息

标题：Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells
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作者：Hiroshi Nakashima ; Quazim A. Alayo ; Pablo Penaloza-MacMaster 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：208
DOI：10.1038/s41598-017-18540-2
语种：English
出版社：Springer Nature
摘要：T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses. We developed a novel mouse glioma model expressing a viral epitope derived from lymphocytic choriomeningitis virus (LCMV), which allowed monitoring of tumor-specific CD8 T-cell responses. These CD8 T cells express high levels of PD-1 and are unable to reject tumors, but this can be reversed by anti-PD-1 treatment. These results suggest the efficacy of PD-1 blockade as a treatment for glioblastoma, an aggressive tumor that results in a uniformly lethal outcome. Importantly, this new syngeneic tumor model may also provide further opportunities to characterize anti-tumor T cell exhaustion and develop novel cancer immunotherapies.