| First Author | Allard B | Year | 2023 |
| Journal | Cell Rep Med | Volume | 4 |
| Issue | 9 | Pages | 101188 |
| PubMed ID | 37729873 | Mgi Jnum | J:348731 |
| Mgi Id | MGI:7642274 | Doi | 10.1016/j.xcrm.2023.101188 |
| Citation | Allard B, et al. (2023) Adenosine A2A receptor is a tumor suppressor of NASH-associated hepatocellular carcinoma. Cell Rep Med 4(9):101188 |
| abstractText | 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. |
