Modulation of myeloid cells by adenosine signaling

Hypoxia, metabolic activity, cell death and immune responses influence the adenosine concentrations in the extracellular space. Cellular responses to hypoxia and inflammation in myeloid cells promote activation of adenosine sensing circuit, which involves increased expression of ectoenzymes that converts phospho-nucleotides such as ATP to adenosine and increased expression of G protein-coupled adenosine receptors. Adenosine sensing circuitry also involves feedforward signaling, which leads to increased expression of hypoxia-inducible factor 1-alpha (HIF1 and feedback signaling, which leads to the suppression of inflammatory transcription factor, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. In this review we will discuss how different subsets of myeloid cells sense adenosine accumulation and how adenosine sensing by myeloid cells influence progression of different immune-related conditions including cancer.