Purinergic regulation of the T cell effector response in the tumor microenvironment
Research area: Mucosal Immunology
Group leaders: Fabio Grassi
- Elisa Civanelli, Master Student
- Benedetta De Ponte Conti , PhD Student
- Tanja Rezzonico Jost, Research assistant
Status: In progress
Peculiar features of the tumor microenvironment condition the function of infiltrating immune system cells and eventually protect the malignant tissue from eradication. Extracellular adenosine triphosphate (eATP) is a signaling molecule, which variably affects directly or after hydrolysis to adenosine, all cells of the immune system. Whereas eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. We found that P2X7 activity in tumor-infiltrating effector T cells limits cell proliferation and tumor suppression. In these cells, deletion of P2rx7, encoding for P2X7, promotes a transcriptional signature that correlates with enhanced cytotoxic T cell response in human solid tumors. Therefore, we address the role of the eATP/P2X7 axis in conditioning the cytotoxic activity of tumor-infiltrating lymphocytes.