Cancer Cell
Volume 30, Issue 3, 12 September 2016, Pages 391-403
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Article
Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses

https://doi.org/10.1016/j.ccell.2016.06.025Get rights and content
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Highlights

  • Functions of CD73 and A2AR are not redundant within the tumor microenvironment

  • Co-targeting CD73 and A2AR reduced tumor initiation, growth, and metastasis

  • Anti-CD73 requires Fc receptor engagement for optimal therapeutic response in mice

Summary

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-γ, 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.

Keywords

immunotherapy
tumor
combination therapy
adenosine
CD73

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