The P2X7 receptor for extracellular ATP: from mediator of inflammation to regulator of tumoral immune infiltration

Adenosine triphosphate (ATP) is well known for its central role in intracellular metabolic processes. However, ATP can also be released in the extracellular space activating two classes of receptors: P2X ion channels and G protein coupled P2Y receptors. Among those, the P2X7 receptor is well characterized for its ability to mediate the production and secretion of IL1β, PGE2 and other inflammatory mediators. P2X7 expression has been reported in a wide range of species including fish, amphibians, birds and mammals. In all these species, the pathogens activating cytokine secretion and phagocytosis. In recent years, we have demonstrated that P2X7 receptor activity can increase intracellular levels of ATP and mediate its secretion. The use of sensors enabling in vivo measurement of extracellular ATP, allowed associating an increase in the peri-cellular levels of the nucleotide with almost all know inflammatory situations, including graft-versus-host disease, allergic and anti-cancer immune reactions. Here we show for the first time that P2X7 receptor also regulates immune infiltrate in cancer. Indeed, when developing experimental melanoma, C57/black 6 mice, lacking P2X7 expression, showed a virtually absent immune infiltrate if compared to wild type controls. The main cells involved seemed to be macrophage-dendritic cells and T lymphocytes, as demonstrated by F/480 and CD3 immunostaining. Taken together all these data suggest a central role for P2X7 receptor in regulating a widespread range of immune responses. receptor is mediating immune response against