Figures & data
Figure 1. Extracellular ATP metabolism in cancer immunosurveillance. (A) Extracellular ATP metabolism from immunostimulatory ATP to immunosuppressive adenosine. ATP is released in an autophagy-dependent manner from tumor cells exposed to immunogenic chemotherapy. Extracellular ATP acts on the nucleotide receptor P2RY2 (Purinergic Receptor P2Y) expressed by dendritic cell (DC) precursors, ultimately leading to recruitment of IFNG (Interferon gamma)-producing cytotoxic T lymphocytes (CTLs) into the tumor bed. (B) Therapeutic improvement of anticancer immunosurveillance by enhancing autophagy leading to an increase in extracellular ATP. (C) Immunostimulation by suppression of the generation of adenosine or depletion of regulatory T cells (Treg). When autophagy is disabled, ATP undergoes 2-step degradation reactions to adenosine through the activity of the ectoATPase ENTPD1/CD39 and the ectonucleotidase NT5E/CD73. Adenosine acts on ADORA1/2 (adenosine A1/2 receptor) expressed by Treg thus mediating immunosuppression. Inhibition of adenosine generation (POM1 [polyoxometalate-1], anti-NT5E/CD73), treatment with an ADORA antagonist (PSB1115) or Treg depletion (anti-IL2R [interleukin 2 receptor], anti-IZUMO1R/FOLR4 [IZUMO1 receptor, JUNO) are therapeutic strategies that reinstate proficient antitumor immunesurveillance.
![Figure 1. Extracellular ATP metabolism in cancer immunosurveillance. (A) Extracellular ATP metabolism from immunostimulatory ATP to immunosuppressive adenosine. ATP is released in an autophagy-dependent manner from tumor cells exposed to immunogenic chemotherapy. Extracellular ATP acts on the nucleotide receptor P2RY2 (Purinergic Receptor P2Y) expressed by dendritic cell (DC) precursors, ultimately leading to recruitment of IFNG (Interferon gamma)-producing cytotoxic T lymphocytes (CTLs) into the tumor bed. (B) Therapeutic improvement of anticancer immunosurveillance by enhancing autophagy leading to an increase in extracellular ATP. (C) Immunostimulation by suppression of the generation of adenosine or depletion of regulatory T cells (Treg). When autophagy is disabled, ATP undergoes 2-step degradation reactions to adenosine through the activity of the ectoATPase ENTPD1/CD39 and the ectonucleotidase NT5E/CD73. Adenosine acts on ADORA1/2 (adenosine A1/2 receptor) expressed by Treg thus mediating immunosuppression. Inhibition of adenosine generation (POM1 [polyoxometalate-1], anti-NT5E/CD73), treatment with an ADORA antagonist (PSB1115) or Treg depletion (anti-IL2R [interleukin 2 receptor], anti-IZUMO1R/FOLR4 [IZUMO1 receptor, JUNO) are therapeutic strategies that reinstate proficient antitumor immunesurveillance.](/cms/asset/5e6bf30a-0466-4131-9a33-4d19da8e1ce6/kaup_a_1214778_f0001_c.gif)
