Extracellular nucleosides and nucleotides as immunomodulators.
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| Abstract |
Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells. In addition, the (over-)production of nucleosides including adenosine by ectonucleotidases located on cancer cells and regulatory T cells can induce immunosuppression, as adenosine directly inhibits the proliferation and activation of effector T cells. Here, we discuss the importance of death metabolites for immunomodulation in general, and the role of the purine nucleotide ATP and its derivative adenosine in particular. In addition, we provide an overview on therapeutic interventions that reinstate tumor immunogenicity in conditions where nucleotide-dependent immunostimulation is obstructed.
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| Authors | Oliver Kepp, Friedemann Loos, Peng Liu, Guido Kroemer |
| Journal | Immunological reviews (Immunol Rev) Vol. 280 Issue 1 Pg. 83-92 (11 2017) ISSN: 1600-065X [Electronic] England |
| PMID | 29027229 (Publication Type: Journal Article, Review) |
| Copyright | © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
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