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Adenosine Signaling in the Tumor Microenvironment

Luca Antonioli1, Matteo Fornai2, Carolina Pellegrini3

  • 1Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. luca.antonioli@medmcs.unipi.it.

Advances in Experimental Medicine and Biology
|October 30, 2020
PubMed

Insights

Extracellular adenosine, produced by dying cancer cells, creates an immunosuppressed tumor environment. Targeting adenosine receptors offers novel therapeutic strategies against cancer.

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • Extracellular adenosine, generated by the CD39/CD73 enzyme axis from ATP released by dying cancer cells, promotes an immunosuppressed tumor microenvironment.
  • This immunosuppression favors tumor onset and progression, creating immune-privileged sites for cancer cell survival.

Purpose of the Study:

  • To elucidate the role of extracellular adenosine in modulating immune and non-immune cells within the tumor microenvironment.
  • To explore adenosine signaling pathways as potential targets for novel cancer therapeutic strategies.

Main Methods:

  • Analysis of adenosine production and degradation pathways in the tumor environment.
  • Investigation of adenosine's interaction with G-protein-coupled receptors (A1, A2A, A2B, A3) on various cell types.
  • Evaluation of adenosine's impact on immune cell function and tumor progression.

Main Results:

  • Adenosine signaling through its receptors plays a critical role in shaping the tumor microenvironment.
  • The CD39/CD73 enzyme axis is central to adenosine generation, contributing to immune suppression.
  • Adenosine influences both immune and non-immune cells, impacting cancer cell proliferation.

Conclusions:

  • Extracellular adenosine is a key mediator of immunosuppression in the tumor microenvironment.
  • Targeting adenosine metabolism or its receptors presents a promising avenue for developing innovative cancer therapies.
  • Understanding adenosine's multifaceted role is crucial for overcoming immune evasion in cancer.
Keywords:
AdenosineAdenosine deaminaseAdenosine receptorsAngiogenesisApoptosisCD39CD73Cell proliferationImmune cellsLymphocytesMetastasisMyeloid cellsNeoplasiaNucleoside transportersTumor microenvironment

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