Details

Autor(en) / Beteiligte

• Todd, Kirsten L.
• Lai, Junyun
• Sek, Kevin
• Huang, Yu-Kuan
• Newman, Dane M.
• Derrick, Emily B.
• Koay, Hui-Fern
• Nguyen, Dat
• Hoang, Thang X.
• Petley, Emma V.
• Chan, Cheok Weng
• Munoz, Isabelle
• House, Imran G.
• Lee, Joel N.
• Kim, Joelle S.
• Li, Jasmine
• Tong, Junming
• N. de Menezes, Maria
• Scheffler, Christina M.
• Yap, Kah Min
• Chen, Amanda X. Y.
• Dunbar, Phoebe A.
• Haugen, Brandon
• Parish, Ian A.
• Johnstone, Ricky W.
• Darcy, Phillip K.
• Beavis, Paul A.

Titel

A2AR eGFP reporter mouse enables elucidation of A2AR expression dynamics during anti-tumor immune responses

Ist Teil von

• Nature communications, 2023-11, Vol.14 (1), p.6990-6990, Article 6990

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Abstract There is significant clinical interest in targeting adenosine-mediated immunosuppression, with several small molecule inhibitors having been developed for targeting the A 2A R receptor. Understanding of the mechanism by which A 2A R is regulated has been hindered by difficulty in identifying the cell types that express A 2A R due to a lack of robust antibodies for these receptors. To overcome this limitation, here an A 2A R eGFP reporter mouse is developed, enabling the expression of A 2A R during ongoing anti-tumor immune responses to be assessed. This reveals that A 2A R is highly expressed on all tumor-infiltrating lymphocyte subsets including Natural Killer (NK) cells, NKT cells, γδ T cells, conventional CD4 + and CD8 + T lymphocytes and on a MHCII hi CD86 hi subset of type 2 conventional dendritic cells. In response to PD-L1 blockade, the emergence of PD-1 + A 2A R - cells correlates with successful therapeutic responses, whilst IL-18 is identified as a cytokine that potently upregulates A 2A R and synergizes with A 2A R deficiency to improve anti-tumor immunity. These studies provide insight into the biology of A 2A R in the context of anti-tumor immunity and reveals potential combination immunotherapy approaches.