Targeting an adenosine-mediated "don't eat me signal" augments anti-lymphoma immunity by anti-CD20 monoclonal antibody.
Adenosine
/ metabolism
Animals
Antibody-Dependent Cell Cytotoxicity
/ immunology
Antigens, CD20
/ metabolism
Antineoplastic Agents, Immunological
/ pharmacology
Apyrase
/ genetics
Biomarkers
Cell Line, Tumor
Disease Models, Animal
Immunomodulation
Immunophenotyping
Kaplan-Meier Estimate
Killer Cells, Natural
/ immunology
Lymphoma
/ drug therapy
Macrophages
/ immunology
Mice
Mice, Knockout
Phagocytosis
/ immunology
Prognosis
Rituximab
/ pharmacology
Signal Transduction
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
07
12
2019
accepted:
18
03
2020
revised:
16
03
2020
pubmed:
10
4
2020
medline:
1
12
2020
entrez:
10
4
2020
Statut:
ppublish
Résumé
A growing body of evidence suggests that macrophage immune checkpoint molecules are potential targets in the era of cancer immunotherapy. Here we showed that extracellular adenosine, an abundant metabolite in the tumor microenvironment, critically impedes the therapeutic efficacy of anti-CD20 monoclonal antibodies (mAbs) against B-cell lymphoma. Using a syngeneic B-cell lymphoma model, we showed that host deficiency of adenosine 2A receptor (A2AR), but not A2BR, remarkably improved lymphoma control by anti-CD20 mAb therapy. Conditional deletion of A2AR in myeloid cells, and to a lesser extent in NK cells, augmented therapeutic efficacy of anti-CD20 mAb. Indeed, adenosine signaling impaired antibody-mediated cellular phagocytosis (ADCP) by macrophages and limited the generation of anti-lymphoma CD8
Identifiants
pubmed: 32269319
doi: 10.1038/s41375-020-0811-3
pii: 10.1038/s41375-020-0811-3
doi:
Substances chimiques
Antigens, CD20
0
Antineoplastic Agents, Immunological
0
Biomarkers
0
Rituximab
4F4X42SYQ6
Apyrase
EC 3.6.1.5
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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