Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas.
Animals
Antineoplastic Agents, Immunological
/ pharmacology
B7-1 Antigen
/ immunology
B7-H1 Antigen
/ immunology
Brain Neoplasms
/ diagnostic imaging
CD8-Positive T-Lymphocytes
/ drug effects
CTLA-4 Antigen
/ antagonists & inhibitors
Cell Line, Tumor
/ transplantation
Disease Models, Animal
Drug Resistance, Neoplasm
/ genetics
Female
Glioma
/ diagnostic imaging
Humans
Macrophages
/ drug effects
Magnetic Resonance Imaging
Male
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Signal Transduction
/ drug effects
T-Lymphocytes, Regulatory
/ drug effects
Tumor Microenvironment
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 02 2020
18 02 2020
Historique:
received:
25
11
2019
accepted:
16
01
2020
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
6
5
2020
Statut:
epublish
Résumé
Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and T
Identifiants
pubmed: 32071302
doi: 10.1038/s41467-020-14642-0
pii: 10.1038/s41467-020-14642-0
pmc: PMC7028933
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-1 Antigen
0
B7-H1 Antigen
0
CTLA-4 Antigen
0
Cd274 protein, mouse
0
Ctla4 protein, mouse
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
931Références
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