Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma.
Animals
Antineoplastic Agents
/ pharmacology
B-Lymphocytes
/ immunology
Brain Neoplasms
/ drug therapy
CD11b Antigen
CD40 Antigens
/ immunology
Cell Line, Tumor
Cytokines
Female
Gene Expression
Glioma
/ drug therapy
Humans
Immunoglobulin G
/ genetics
Immunotherapy
Male
Mice
Mice, Inbred C57BL
Myeloid Cells
Phenotype
T-Lymphocytes
Tertiary Lymphoid Structures
/ immunology
Tumor Microenvironment
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 07 2021
05 07 2021
Historique:
received:
28
01
2021
accepted:
09
06
2021
entrez:
6
7
2021
pubmed:
7
7
2021
medline:
27
7
2021
Statut:
epublish
Résumé
Gliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-naïve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of αCD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b
Identifiants
pubmed: 34226552
doi: 10.1038/s41467-021-24347-7
pii: 10.1038/s41467-021-24347-7
pmc: PMC8257767
doi:
Substances chimiques
Antineoplastic Agents
0
CD11b Antigen
0
CD40 Antigens
0
Cytokines
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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