Abstract
Adenosine suppresses the production of various cytokines/ chemokines and inhibits the cytotoxic activity of murine and human NK cells activated with IL-2 or Ly49D, NKp46-receptor crosslinking, respectively. These effects are mediated by the type A2A adenosine receptor via stimulation of adenylyl cyclase, increased production of cAMP, and activation of PKA. PKA I, but not PKA II, participates in the inhibitory effects of adenosine. Blocking regulatory, but not catalytic, subunits of PKA I abrogates the inhibitory effects of adenosine. These findings suggest that tumor-produced adenosine inhibits the activity of NK and other effector cells and thereby protects tumors from immune-mediated destruction.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Adenosine / immunology*
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Adenosine / metabolism
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Animals
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Cyclic AMP-Dependent Protein Kinases / immunology*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cytokines / biosynthesis
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Cytotoxicity, Immunologic
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Humans
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Interleukin-2 / metabolism
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Isoenzymes / immunology
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Isoenzymes / metabolism
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Membrane Glycoproteins / metabolism
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Natural Cytotoxicity Triggering Receptor 1
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Neoplasms / immunology
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Receptors, Adenosine A2 / immunology*
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Receptors, Adenosine A2 / metabolism
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Receptors, Immunologic / metabolism
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Tumor Escape*
Substances
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Cytokines
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Interleukin-2
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Isoenzymes
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Membrane Glycoproteins
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NCR1 protein, human
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Natural Cytotoxicity Triggering Receptor 1
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Receptors, Adenosine A2
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Receptors, Immunologic
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Cyclic AMP-Dependent Protein Kinases
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Adenosine