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Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity

1
The Postgraduate Biosciences Program, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, RS Brazil
2
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
3
UPMC Hillman Cancer, Pittsburgh, PA 15213, USA
4
Departments of Immunology and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5698; https://doi.org/10.3390/ijms20225698
Received: 14 October 2019 / Revised: 4 November 2019 / Accepted: 12 November 2019 / Published: 14 November 2019
(This article belongs to the Section Molecular Immunology)
The adenosine pathway plays a key role in modulating immune responses in physiological and pathological conditions. Physiologically, anti-inflammatory effects of adenosine balance pro-inflammatory adenosine 5’-triphosphate (ATP), protecting tissues from damage caused by activated immune cells. Pathologically, increased adenosine monophosphatase (AMPase) activity in tumors leads to increased adenosine production, generating a deeply immunosuppressed microenvironment and promoting cancer progression. Adenosine emerges as a promising target for cancer therapy. It mediates protumor activities by inducing tumor cell proliferation, angiogenesis, chemoresistance, and migration/invasion by tumor cells. It also inhibits the functions of immune cells, promoting the formation of a tumor-permissive immune microenvironment and favoriting tumor escape from the host immune system. Pharmacologic inhibitors, siRNA or antibodies specific for the components of the adenosine pathway, or antagonists of adenosine receptors have shown efficacy in pre-clinical studies in various in vitro and in vivo tumor models and are entering the clinical arena. Inhibition of the adenosine pathway alone or in combination with classic immunotherapies offers a potentially effective therapeutic strategy in cancer. View Full-Text
Keywords: cancer; adenosine; CD73; immune system cancer; adenosine; CD73; immune system
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MDPI and ACS Style

Azambuja, J.H.; Ludwig, N.; Braganhol, E.; Whiteside, T.L. Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity. Int. J. Mol. Sci. 2019, 20, 5698.

AMA Style

Azambuja JH, Ludwig N, Braganhol E, Whiteside TL. Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity. International Journal of Molecular Sciences. 2019; 20(22):5698.

Chicago/Turabian Style

Azambuja, Juliana H.; Ludwig, Nils; Braganhol, Elizandra; Whiteside, Theresa L. 2019. "Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity" Int. J. Mol. Sci. 20, no. 22: 5698.

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