Tissue- and temporal-specific roles of extracellular ATP on T cell metabolism and function

Abstract

The activation and function of T cells is fundamental for the control of infectious diseases and cancer, and conversely can mediate several autoimmune diseases. Among the signaling pathways leading to T cell activation and function, the sensing of extracellular adenosine triphosphate (eATP) has been recently appreciated as an important component. Through a plethora of purinergic receptors, most prominently P2RX7, eATP sensing can induce a wide variety of processes in T cells, such as proliferation, subset differentiation, survival, or cell death. The downstream roles of eATP sensing can vary according to (a) the T cell subset, (b) the tissue where T cells are, and (c) the time after antigen exposure. In this mini-review, we revisit the recent findings on how eATP signaling pathways regulate T-cell immune responses and posit important unanswered questions on this field.

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

“…P2X7 positively affects tumor infiltration via CD4 + T helper effector cells [15]. ADO via A2AR reduces cytotoxic cell activity [148,149], while P2X7 increases their metabolic activity, thus sustaining responses mediated by memory cells [88]. The TME is rich in eATP due to necrosis and active release of the nucleotide.…”

“…This picture is further complicated by the effects that, via P2X7, eATP exerts on different T cell populations, including effector and regulatory T cells, their ability to survive as memory cells, and exhaustion or senescence processes [ 12 , 13 , 88 ]. For example, two research groups proposed exploiting P2X7 activity in tumor-infiltrating cytotoxic T cells to improve adoptive cell therapy potential, but achieved opposing results [ 14 , 89 ].…”