Journal article

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

Kirsten L Todd, Junyun Lai, Kevin Sek, Yu-Kuan Huang, Dane M Newman, Emily B Derrick, Hui-Fern Koay, Dat Nguyen, Thang X Hoang, Emma V Petley, Cheok Weng Chan, Isabelle Munoz, Imran G House, Joel N Lee, Joelle S Kim, Jasmine Li, Junming Tong, Maria N. de Menezes, Christina M Scheffler, Kah Min Yap Show all

Nature Communications | Nature Portfolio | Published : 2023

Abstract

There is significant clinical interest in targeting adenosine-mediated immunosuppression, with several small molecule inhibitors having been developed for targeting the A2AR receptor. Understanding of the mechanism by which A2AR is regulated has been hindered by difficulty in identifying the cell types that express A2AR due to a lack of robust antibodies for these receptors. To overcome this limitation, here an A2AR eGFP reporter mouse is developed, enabling the expression of A2AR during ongoing anti-tumor immune responses to be assessed. This reveals that A2AR is highly expressed on all tumor-infiltrating lymphocyte subsets including Natural Killer (NK) cells, NKT cells, γδ T cells, convent..

View full abstract

Grants

Awarded by The authors would like to acknowledge Prof. Dale Godfrey who provide access to the alphaGal-Cer tetramer used in the study. This work was funded by a Program Grant from the National Health and Medical Research Council (NHMRC; Grant number 1132373). P.A.B


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Victorian Cancer Agency Mid-Career Fellowship


Awarded by Victorian Cancer Agency Early Career Fellowship


Awarded by NHMRC Senior Research Fellowship


Funding Acknowledgements

The authors would like to acknowledge Prof. Dale Godfrey who provide access to the alpha Gal-Cer tetramer used in the study. This work was funded by a Program Grant from the National Health and Medical Research Council (NHMRC; Grant number 1132373). P.A.B. was supported by a National Breast Cancer Foundation Fellowship (ID# ECF-17-005, 2017-2020) and a Victorian Cancer Agency Mid-Career Fellowship (2021-Current). I.G. House was supported by a Victorian Cancer Agency Early Career Fellowship (ECRF20017). P.K.D. was supported by an NHMRC Senior Research Fellowship (APP1136680). Junyun Lai was a recipient of a US Cancer Research Institute Irvington postdoctoral fellowship (award no. 3530). The authors wish to acknowledge the contributions of Ms Karen Gill, Mr Mike Rear and Mr Graeme Sissing who act as consumer representatives for the laboratory.