VLM catecholaminergic neurons control tumor growth by regulating CD8+ T cells.
Proc Natl Acad Sci U S A
; 118(28)2021 07 13.
Article
em En
| MEDLINE
| ID: mdl-34260392
ABSTRACT
It is known that tumor growth can be influenced by the nervous system. It is not known, however, if tumors communicate directly with the central nervous system (CNS) or if such interactions may impact tumor growth. Here, we report that ventrolateral medulla (VLM) catecholaminergic (CA) neurons in the mouse brain are activated in tumor-bearing mice and the activity of these neurons significantly alter tumor growth in multiple syngeneic and spontaneous mouse tumor models. Specific ablation of VLM CA neurons by a dopamine-ß-hydroxylase (DBH) promotor-activated apoptosis-promoting caspase-3 in Dbh-Cre mice as well as inhibition of these neurons by a chemogenetic method slowed tumor progression. Consistently, chemogenetic activation of VLM CA neurons promoted tumor growth. The tumor inhibition effect of VLM CA neuron ablation is mitigated in Dbh-Cre;Rag1-/- mice, indicating that this regulatory effect is mediated by the adaptive immune system. Specific depletion of CD8+ T cells using an anti-CD8+ antibody also mitigated the tumor suppression resulting from the VLM CA neuron ablation. Finally, we showed that the VLM CA neuronal ablation had an additive antitumor effect with paclitaxel treatment. Collectively, our study uncovered the role of VLM CA neurons in the mouse brain in controlling tumor growth in the mouse body.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bulbo
/
Catecolaminas
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Linfócitos T CD8-Positivos
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China