Adenosine A2A receptor is a tumor suppressor of NASH-associated hepatocellular carcinoma.
Cell Rep Med
; 4(9): 101188, 2023 09 19.
Article
em En
| MEDLINE
| ID: mdl-37729873
ABSTRACT
Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions of A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion in mice triggers obesity, non-alcoholic steatohepatitis (NASH), and systemic inflammation, leading to spontaneous HCC and promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine (DEN)-induced HCC. Conditional Adora2a deletion reveals critical roles of myeloid and hepatocyte-derived A2AR signaling in restraining HCC by limiting hepatic inflammation and steatosis. Remarkably, the impact of A2AR pharmacological blockade on HCC development is dependent on pre-existing NASH. In support of our animal studies, low ADORA2A gene expression in human HCC is associated with cirrhosis, hepatic inflammation, and poor survival. Together, our study uncovers a previously unappreciated tumor-suppressive function for A2AR in the liver and suggests caution in the use of A2AR antagonists in patients with NASH and NASH-associated HCC.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Hepatopatia Gordurosa não Alcoólica
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Neoplasias Hepáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2023
Tipo de documento:
Article