CCRL2 promotes antitumor T-cell immunity via amplifying TLR4-mediated immunostimulatory macrophage activation.
Animals
CD8-Positive T-Lymphocytes
/ immunology
China
Female
Immunization
Macrophage Activation
/ immunology
Male
Melanoma
/ metabolism
Mice
NF-kappa B
/ metabolism
Neoplasms
/ genetics
Receptors, CCR
/ genetics
Signal Transduction
T-Lymphocytes
/ metabolism
Toll-Like Receptor 4
/ immunology
Tumor-Associated Macrophages
/ immunology
CCRL2
TLR4
antitumor T-cell immunity
tumor associated macrophages
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
20 04 2021
20 04 2021
Historique:
entrez:
13
4
2021
pubmed:
14
4
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Macrophages are the key regulator of T-cell responses depending on their activation state. C-C motif chemokine receptor-like 2 (CCRL2), a nonsignaling atypical receptor originally cloned from LPS-activated macrophages, has recently been shown to regulate immune responses under several inflammatory conditions. However, whether CCRL2 influences macrophage function and regulates tumor immunity remains unknown. Here, we found that tumoral CCRL2 expression is a predictive indicator of robust antitumor T-cell responses in human cancers. CCRL2 is selectively expressed in tumor-associated macrophages (TAM) with immunostimulatory phenotype in humans and mice. Conditioned media from tumor cells could induce CCRL2 expression in macrophages primarily via TLR4, which is negated by immunosuppressive factors.
Identifiants
pubmed: 33846258
pii: 2024171118
doi: 10.1073/pnas.2024171118
pmc: PMC8072249
pii:
doi:
Substances chimiques
Ccrl2 protein, mouse
0
NF-kappa B
0
Receptors, CCR
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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