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Monitoring the Cancer-Immunity Cycle and Exploring Tumor Microenvironment Dynamics
Published on: June 7, 2024
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ATP and cancer immunosurveillance
Oliver Kepp1,2, Lucillia Bezu1,2, Takahiro Yamazaki3
1Equipe labellisée par la Ligue contre le cancer, Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université de Paris, Paris, France.
The EMBO Journal
|June 14, 2021
Summary
Extracellular adenosine triphosphate (ATP) and its metabolites act as crucial signaling molecules in the tumor microenvironment (TME). Understanding purinergic signaling is key to targeting cancer immunosurveillance and developing new therapies.
Area of Science:
- Immunology
- Cancer Biology
- Biochemistry
Background:
- Intracellular adenosine triphosphate (ATP) is vital for cellular energy metabolism within the tumor microenvironment (TME).
- Extracellular ATP functions as a potent signaling molecule, influencing TME biology through purinergic signaling pathways.
- The biological impact of extracellular ATP is modulated by receptor interactions, cell types, regulatory circuits, and ectonucleotidase activity.
Purpose of the Study:
- To elucidate the molecular and cellular mechanisms of how extracellular ATP and its metabolites affect cancer immunosurveillance.
- To identify and discuss therapeutically targetable pathways within the purinergic signaling network of the TME.
Main Methods:
- Review of molecular mechanisms governing ATP signaling in the TME.
- Analysis of cellular interactions and regulatory circuitries involved in purinergic signaling.
- Examination of ectonucleotidase activity and metabolite-mediated effects.
Main Results:
- Extracellular ATP and its breakdown products significantly influence cancer immunosurveillance.
- Specific receptors, cell types, and regulatory circuits dictate the net effects of purinergic signaling.
- Ectonucleotidases rapidly catabolize extracellular ATP, generating metabolites with distinct biological functions.
Conclusions:
- Targeting extracellular ATP metabolism and purinergic signaling pathways presents a promising therapeutic strategy for enhancing cancer immunosurveillance.
- A comprehensive understanding of these complex mechanisms is crucial for developing effective immunotherapies.
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