Anti-PD-1 Induces M1 Polarization in the Glioma Microenvironment and Exerts Therapeutic Efficacy in the Absence of CD8 Cytotoxic T Cells.
Animals
Brain Neoplasms
/ drug therapy
CD8-Positive T-Lymphocytes
/ immunology
Cell Line, Tumor
/ transplantation
Disease Models, Animal
Glioblastoma
/ drug therapy
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Immunity, Innate
/ drug effects
Macrophage Activation
/ drug effects
Mice
Mice, Transgenic
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Tumor Microenvironment
/ drug effects
Tumor-Associated Macrophages
/ drug effects
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
19
12
2019
revised:
16
04
2020
accepted:
11
06
2020
pubmed:
20
6
2020
medline:
26
11
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated inconsistent therapeutic results in patients with glioblastoma (GBM) including those with profound impairments in CD8 T-cell effector responses. We ablated the We observed a survival benefit in immunocompetent mice with endogenously arising intracranial glioblastomas after intravenous administration of anti-PD-1. The therapeutic effect of PD-1 administration persisted in mice even after genetic ablation of the CD8 gene (CD8 Our results show that the therapeutic effect of anti-PD-1 blockade in GBM may be mediated by the innate immune system, rather than by CD8 T cells. Anti-PD-1 immunologically modulates innate immunity in the glioma microenvironment-likely a key mode of activity.
Identifiants
pubmed: 32554515
pii: 1078-0432.CCR-19-4110
doi: 10.1158/1078-0432.CCR-19-4110
pmc: PMC7483850
mid: NIHMS1605411
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4699-4712Subventions
Organisme : NCI NIH HHS
ID : R01 CA120813
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127001
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS094615
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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