Evaluation of P2X7 Receptor Function in Tumor Contexts Using rAAV Vector and Nanobodies (AAVnano)
Mélanie Demeules1, Allan Scarpitta1, Catalina Abad1
1Normandie University, UNIROUEN, INSERM, U1234, Pathophysiology, Autoimmunity, Neuromuscular Diseases and Regenerative THERapies, Rouen, France.
Abstract:
Adenosine triphosphate (ATP) represents a danger signal that accumulates in injured tissues, in inflammatory sites, and in the tumor microenvironment. Extracellular ATP is known to signal through plasma membrane receptors of the P2Y and P2X families. Among the P2X receptors, P2X7 has attracted increasing interest in the field of inflammation as well as in cancer. P2X7 is expressed by immune cells and by most malignant tumor cells where it plays a crucial yet complex role that remains to be clarified. P2X7 activity has been associated with production and release of pro-inflammatory cytokines, modulation of the activity and survival of immune cells, and the stimulation of proliferation and migratory properties of tumor cells. Hence, P2X7 plays an intricate role in the tumor microenvironment combining beneficial and detrimental effects that need to be further investigated. For this, we developed a novel methodology termed AAVnano based on the use of Adeno-associated viral vectors (AAV) encoding nanobodies targeting P2X7. We discuss here the advantages of this tool to study the different functions of P2X7 in cancer and other pathophysiological contexts.
Insights
Extracellular adenosine triphosphate (ATP) signals via P2X7 receptors, crucial in inflammation and cancer. A novel Adeno-associated viral vector (AAV) nanobody tool (AAVnano) aids P2X7 research in the tumor microenvironment.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Extracellular adenosine triphosphate (ATP) acts as a danger signal in various pathological conditions, including inflammation and cancer.
- ATP signals through P2Y and P2X receptor families, with P2X7 gaining significant attention for its role in immune responses and tumorigenesis.
- P2X7 receptors are expressed on immune cells and malignant cells, exhibiting complex functions in the tumor microenvironment, including cytokine release and tumor cell proliferation.
Purpose of the Study:
- To investigate the multifaceted role of P2X7 receptors in inflammation and cancer.
- To introduce and validate a novel research tool for studying P2X7 functions.
Main Methods:
- Development of a novel methodology, AAVnano, utilizing Adeno-associated viral vectors (AAV) that encode nanobodies.
- The AAVnano system is designed to specifically target and study the P2X7 receptor.
Main Results:
- The AAVnano tool provides a novel approach to investigate P2X7 functions.
- This methodology facilitates the study of P2X7's complex roles in the tumor microenvironment and other diseases.
Conclusions:
- P2X7 receptor signaling is integral to both inflammatory processes and cancer progression.
- The AAVnano tool offers significant advantages for dissecting the intricate functions of P2X7 in various pathophysiological contexts, including cancer research.
