The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Extracellular adenosine (eADO) and extracellular ATP (eATP) are key signaling molecules in the tumor microenvironment (TME).
• eATP promotes inflammation via P2 receptors, while eADO generally mediates immunosuppression through P1 receptors.
• The balance between eATP and eADO influences immune cell function and tumor immunity.

Purpose of the Study:

• To review the current understanding of the tumor adenosinergic system.
• To explore the roles of purinergic receptors (P1 and P2) in various cell types within the TME.
• To discuss potential future adenosinergic-based therapies for immuno-oncology.

Main Methods:

• Literature review of current research on the adenosinergic system in cancer.
• Analysis of the signaling pathways involving extracellular adenosine and ATP.
• Discussion of therapeutic strategies targeting purinergic receptors in immuno-oncology.

Main Results:

• Extracellular adenosine signaling is a critical regulator of tumor immunity.
• Hydrolysis of eATP to eADO shifts the balance towards immunosuppression in the TME.
• Purinergic receptors (P1 and P2) on immune, tumor, and stromal cells modulate the tumor immune response.

Conclusions:

• The tumor adenosinergic system, involving eATP and eADO, significantly impacts immune surveillance.
• Targeting adenosinergic pathways offers promising avenues for novel immuno-oncology treatments.
• Further research into the complex interactions within the TME is crucial for therapeutic development.