Research Paper Volume 12, Issue 15 pp 15290—15301
Neutrophil depletion enhances the therapeutic effect of PD-1 antibody on glioma
- 1 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China
- 2 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- 3 Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing, China
Received: December 17, 2019 Accepted: May 25, 2020 Published: August 4, 2020https://doi.org/10.18632/aging.103428
How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.
Tumor-infiltrating neutrophils (TINs), the predominant leukocytes in the tumor microenvironment, are important for cancer-related immunosuppression. Combinations of multiple immune checkpoint inhibitors can significantly improve outcomes in murine glioma models. Here, we investigated TIN levels in human glioma samples and tested the antitumor efficacy of neutrophil depletion alone or in combination with an anti-programmed death 1 (PD-1) antibody. To investigate the clinical relevance, we determined the correlation between tumor grade or survival and TIN levels in 202 resected glioma specimens. TCGA and CGGA data were used to validate the results and analyze the biological functions of TINs in gliomas. An orthotopic xenograft glioma mouse model was used to study the therapeutic effect of anti-PD-1 and/or anti-ly6G. Decreased TIN levels correlated with lower grades, mutant isocitrate dehydrogenase, and favorable prognosis, which was validated by CGGA and TCGA dataset results. Bioinformatics analysis revealed that TINs are mainly involved in angiogenic, inflammatory, and interferon-γ responses in gliomas. TINs were positively correlated with programmed death ligand-1 expression. In xenograft models, combined anti-PD-1 and neutrophil depletion therapy significantly inhibited tumor growth and promoted survival. This study demonstrates that TINs were related to glioma tumorigenesis. Targeting neutrophils could thus enhance the therapeutic effect of PD-1 blockade for gliomas.