The adenosine pathway in immuno-oncology

doi:10.1038/s41571-020-0382-2

Review

. 2020 Oct;17(10):611-629.

doi: 10.1038/s41571-020-0382-2. Epub 2020 Jun 8.

The adenosine pathway in immuno-oncology

Bertrand Allard^{1

2}, David Allard^{1

2}, Laurence Buisseret³, John Stagg^{4

5}

Affiliations

¹ Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
² Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
³ Department of Medical Oncology, Institut Jules Bordet, Brussels, Belgium.
⁴ Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. john.stagg@umontreal.ca.
⁵ Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada. john.stagg@umontreal.ca.

PMID: 32514148
DOI: 10.1038/s41571-020-0382-2

Review

The adenosine pathway in immuno-oncology

Bertrand Allard et al. Nat Rev Clin Oncol. 2020 Oct.

. 2020 Oct;17(10):611-629.

doi: 10.1038/s41571-020-0382-2. Epub 2020 Jun 8.

Authors

Bertrand Allard^{1

2}, David Allard^{1

2}, Laurence Buisseret³, John Stagg^{4

5}

Affiliations

¹ Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
² Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
³ Department of Medical Oncology, Institut Jules Bordet, Brussels, Belgium.
⁴ Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. john.stagg@umontreal.ca.
⁵ Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada. john.stagg@umontreal.ca.

PMID: 32514148
DOI: 10.1038/s41571-020-0382-2

Erratum in

Publisher Correction: The adenosine pathway in immuno-oncology.
Allard B, Allard D, Buisseret L, Stagg J. Allard B, et al. Nat Rev Clin Oncol. 2020 Oct;17(10):650. doi: 10.1038/s41571-020-0415-x. Nat Rev Clin Oncol. 2020. PMID: 32681060

Abstract

Cancer immunotherapy based on immune-checkpoint inhibition or adoptive cell therapy has revolutionized cancer care. Nevertheless, a large proportion of patients do not benefit from such treatments. Over the past decade, remarkable progress has been made in the development of 'next-generation' therapeutics in immuno-oncology, with inhibitors of extracellular adenosine (eADO) signalling constituting an expanding class of agents. Induced by tissue hypoxia, inflammation, tissue repair and specific oncogenic pathways, the adenosinergic axis is a broadly immunosuppressive pathway that regulates both innate and adaptive immune responses. Inhibition of eADO-generating enzymes and/or eADO receptors can promote antitumour immunity through multiple mechanisms, including enhancement of T cell and natural killer cell function, suppression of the pro-tumourigenic effects of myeloid cells and other immunoregulatory cells, and promotion of antigen presentation. With several clinical trials currently evaluating inhibitors of the eADO pathway in patients with cancer, we herein review the pathophysiological function of eADO with a focus on effects on antitumour immunity. We also discuss the treatment opportunities, potential limitations and biomarker-based strategies related to adenosine-targeted therapy in oncology.

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References

1. Wolberg, G., Zimmerman, T. P., Hiemstra, K., Winston, M. & Chu, L. C. Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. Science 187, 957–959 (1975). - PubMed
1. Henney, C. S., Bourne, H. R. & Lichtenstein, L. M. The role of cyclic 3′,5′ adenosine monophosphate in the specific cytolytic activity of lymphocytes. J. Immunol. 108, 1526–1534 (1972). - PubMed
1. Strom, T. B., Deisseroth, A., Morganroth, J., Carpenter, C. B. & Merrill, J. P. Alteration of the cytotoxic action of sensitized lymphocytes by cholinergic agents and activators of adenylate cyclase. Proc. Natl Acad. Sci. USA 69, 2995–2999 (1972). - PubMed
1. Blay, J., White, T. D. & Hoskin, D. W. The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res. 57, 2602–2605 (1997). - PubMed
1. Ohta, A. & Sitkovsky, M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414, 916–920 (2001). - PubMed

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[1] Wolberg, G., Zimmerman, T. P., Hiemstra, K., Winston, M. & Chu, L. C. Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. Science 187, 957–959 (1975). - PubMed

[2] Wolberg, G., Zimmerman, T. P., Hiemstra, K., Winston, M. & Chu, L. C. Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. Science 187, 957–959 (1975). - PubMed

[3] Henney, C. S., Bourne, H. R. & Lichtenstein, L. M. The role of cyclic 3′,5′ adenosine monophosphate in the specific cytolytic activity of lymphocytes. J. Immunol. 108, 1526–1534 (1972). - PubMed

[4] Henney, C. S., Bourne, H. R. & Lichtenstein, L. M. The role of cyclic 3′,5′ adenosine monophosphate in the specific cytolytic activity of lymphocytes. J. Immunol. 108, 1526–1534 (1972). - PubMed

[5] Strom, T. B., Deisseroth, A., Morganroth, J., Carpenter, C. B. & Merrill, J. P. Alteration of the cytotoxic action of sensitized lymphocytes by cholinergic agents and activators of adenylate cyclase. Proc. Natl Acad. Sci. USA 69, 2995–2999 (1972). - PubMed

[6] Strom, T. B., Deisseroth, A., Morganroth, J., Carpenter, C. B. & Merrill, J. P. Alteration of the cytotoxic action of sensitized lymphocytes by cholinergic agents and activators of adenylate cyclase. Proc. Natl Acad. Sci. USA 69, 2995–2999 (1972). - PubMed

[7] Blay, J., White, T. D. & Hoskin, D. W. The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res. 57, 2602–2605 (1997). - PubMed

[8] Blay, J., White, T. D. & Hoskin, D. W. The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res. 57, 2602–2605 (1997). - PubMed

[9] Ohta, A. & Sitkovsky, M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414, 916–920 (2001). - PubMed

[10] Ohta, A. & Sitkovsky, M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414, 916–920 (2001). - PubMed

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The adenosine pathway in immuno-oncology

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The adenosine pathway in immuno-oncology

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