P2RX7B is a new theranostic marker for lung adenocarcinoma patients
Jonathan Benzaquen, Serena Janho Dit Hreich, Simon Heeke, Thierry Juhel, Salomé Lalvee, Serge Bauwens, Simona Saccani, Philippe Lenormand, Véronique Hofman, Mathilde Butori, Sylvie Leroy, Jean-Philippe Berthet, Charles-Hugo Marquette, Paul Hofman, Valérie Vouret-Craviari
Abstract
Rationale:The characterization of new theranostic biomarkers is crucial to improving the clinical outcome of patients with advanced lung cancer.Here, we aimed at characterizing the P2RX7 receptor, a positive modulator of the anti-tumor immune response, in patients with lung adenocarcinoma.Methods: The expression of P2RX7 and its splice variants was analyzed by RT-qPCR using areas of tumor and non-tumor lung adenocarcinoma (LUAD) tissues on both immune and non-immune cells.The biological activity of P2RX7 was studied by flow cytometry using fluorescent dyes.Bi-molecular fluorescence complementation and confocal microscopy were used to assess the oligomerization of P2RX7.Tumor immune infiltrates were characterized by immunohistochemistry. Results: Fifty-three patients with LUAD were evaluated.P2RX7A, and 3 alternative splice variants were expressed in LUAD tissues and expression was down regulated in tumor versus adjacent non-tumor tissues.The protein retained biological activity only in immune cells.The P2RX7B splice variant was differentially upregulated in immune cells (P < 0.001) of the tumor and strong evidence of oligomerization of P2RX7A and B was observed in the HEK expression model, which correlated with a default in the activity of P2RX7.Finally, LUAD patients with a high level of P2RX7B had non-inflamed tumors (P = 0.001).Conclusion: Our findings identified P2RX7B as a new theranostic tool to restore functional P2RX7 activity and open alternative therapeutic opportunities to improve LUAD patient outcome.