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Sci Rep. 2018 Jan 9;8(1):208. doi: 10.1038/s41598-017-18540-2.

Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells.

Author information

1
Harvey W. Cushing Neuro-oncology Laboratories (HCNL), Department of Neurosurgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA. HNakashima@bwh.harvard.edu.
2
Harvey W. Cushing Neuro-oncology Laboratories (HCNL), Department of Neurosurgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA.
3
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Boston, MA, 02115, USA.
5
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA.
6
Center for Neuro-Oncology, Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Boston, MA, 02115, USA.
7
Center for Biostatistics, The Ohio State University, Columbus, Ohio, 43210, USA.
8
Comprehensive Cancer Center, and Division of Hematology in Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, 43210, USA.
9
Harvey W. Cushing Neuro-oncology Laboratories (HCNL), Department of Neurosurgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA. EAChiocca@bwh.harvard.edu.

Abstract

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.

PMID:
29317703
PMCID:
PMC5760520
DOI:
10.1038/s41598-017-18540-2
[Indexed for MEDLINE]
Free PMC Article

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