Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells
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CitationNakashima, Hiroshi, Quazim A. Alayo, Pablo Penaloza-MacMaster, Gordon J. Freeman, Vijay K. Kuchroo, David A. Reardon, Soledad Fernandez, Michael Caligiuri, and E. Antonio Chiocca. 2018. “Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells.” Scientific Reports 8 (1): 208. doi:10.1038/s41598-017-18540-2. http://dx.doi.org/10.1038/s41598-017-18540-2.
AbstractT 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.
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