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ENTPD1/CD39 is a promising therapeutic target in oncology

Oncogene volume 32, pages 1743–1751 (2013)Cite this article

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Abstract

Regulatory T cells (Tregs) are a subpopulation of CD4+ T cells that are essential for maintaining the homeostasis of the immune system, limiting self-reactivity and excessive immune responses against foreign antigens. In cancer, infiltrated Tregs inhibit the effector lymphocytes and create a favorable environment for the growth of the tumor. Although Tregs mediate immunosuppression through multiple, non-redundant, cell-contact dependent and independent mechanisms, a growing body of evidence suggests an important role for the CD39–CD73–adenosine pathway. CD39 ectonucleotidase is the rate-limiting enzyme of a cascade leading to the generation of suppressive adenosine that alters CD4 and CD8 T cell and natural killer cell antitumor activities. Here, we review the recent literature supporting CD39 as a promising therapeutic target in oncology. In vitro and in vivo experiments involving knockout models and surrogate inhibitors of CD39 provide evidence in support of the anticancer activity of CD39 inhibition and predict a favorable safety profile for CD39 inhibitory compounds. In addition, we report the ongoing development of CD39-blocking monoclonal antibodies as potential anticancer drugs. Indeed, CD39 antagonistic antibodies could represent novel therapeutic tools for selectively inhibiting Treg function without depletion, a major limitation of current Treg-targeting strategies.

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Acknowledgements

We would like to acknowledge our collaborators, Dr Patrice Hémon, INSERM UMR-S 976 and Ms Caroline Laheurte, INSERM U851. This work was supported by an INSERM and ANR grant (Emergence-BIO 2008 awarded to AB) and OSEO (OSEO aide au transfert awarded to NB).

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Authors and Affiliations

  1. OREGA Biotech, L’espace Européen, Ecully, France

    J Bastid, A Cottalorda-Regairaz & G Alberici

  2. Université de Lyon, Lyon, France

    N Bonnefoy

  3. INSERM, U851, Lyon, France

    N Bonnefoy & J-F Eliaou

  4. Université Lyon 1, UMS3444/US8, Lyon, France

    N Bonnefoy & J-F Eliaou

  5. Département d’Immunologie, Centre Hospitalier Régional Universitaire de Montpellier et Faculté de Médecine Université Montpellier 1, Montpellier, France

    J-F Eliaou

  6. Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 976, Paris, France

    A Bensussan

  7. Université Paris Diderot, Sorbonne Paris Cité, Laboratory of Immunology, Dermatology & Oncology, Paris, France

    A Bensussan

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Drs Bonnefoy, Bensussan, Alberici and Eliaou are cofounders and shareholders of OREGA Biotech. Dr Bastid is an employee of OREGA Biotech. Dr Cottalorda-Regairaz declares no conflict of interest.

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Bastid, J., Cottalorda-Regairaz, A., Alberici, G. et al. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene 32, 1743–1751 (2013). https://doi.org/10.1038/onc.2012.269

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