Journal of Molecular Medicine

, Volume 96, Issue 9, pp 903–913 | Cite as

Adenosinergic signaling as a target for natural killer cell immunotherapy

  • Jiao Wang
  • Sandro Matosevic


Purinergic signaling through adenosine plays a key role in immune regulation. Hypoxia-driven accumulation of extracellular adenosine results in the generation of an immunosuppressive niche that fuels tumor development. Such immunometabolic modulation has shown to be a promising therapeutic target through blockade of adenosine receptors which mediate adenosine’s immunosuppressive function, or cancer-associated ectonucleotidases CD39 and CD73 that catalyze the synthesis of adenosine. Adenosinergic signaling heavily implicates natural killer cells through both direct and indirect effects on their cytolytic activity, expression of cytotoxic granules, interferon-γ, and activating receptors. Continuing work has uncovered multiple checkpoints linked to adenosine within the purinergic signaling cascade as contributing to immune evasion from NK cell effector function. Here, we discuss these checkpoints and the recent body of work that focuses on adenosinergic signaling as a target for natural killer cell of cancer.


Adenosinergic signaling Cancer Natural killer cell immunotherapy Immunometabolism 


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Industrial and Physical PharmacyPurdue UniversityWest LafayetteUSA
  2. 2.Purdue Center for Cancer ResearchPurdue UniversityWest LafayetteUSA

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