Abstract

Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-gamma, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors. In a two-way mixed leukocyte reaction using a fully human anti-CD73, we demonstrated that Fc receptor binding augmented the production of proinflammatory cytokines.

Authors	Young, Arabella; Ngiow, Shin Foong; Barkauskas, Deborah S.; Sult, Erin; Hay, Carl; Blake, Stephen J.; Huang, Qihui; Liu, Jing; Takeda, Kazuyoshi; Teng, Michele W. L.; Sachsenmeier, Kris; Smyth, Mark J.
Journal	CANCER CELL
Pages	391-403
Volume	30
Date	1/09/2016
Grant ID	1078671
Funding Body	NHMRC
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.ccell.2016.06.025
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