期刊
NATURE MEDICINE
卷 25, 期 3, 页码 477-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-018-0337-7
关键词
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资金
- National Institutes of Health SPORE in Brain Cancer [P50CA211015]
- Parker Institute for Cancer Immunotherapy [20163828]
- Cancer Research Institute
- Musella Foundation
- Ben and Catherine Ivy Foundation
- Uncle Kory Foundation
- Defeat GBM Program of the National Brain Tumor Society
- Ziering Family Foundation
- Merck Co., Inc.
- Adaptive Biotechnologies
Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell-and interferon-gamma-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.
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