ENTPD1/CD39 is a promising therapeutic target in oncology.

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.

TWISTing an embryonic transcription factor into an oncoprotein.

Over the past decade, the reactivation of TWIST embryonic transcription factors has been described as a frequent event and a marker of poor prognosis in an impressive array of human cancers. Growing evidence now supports the premise that these cancers hijack TWIST's embryonic functions, granting oncogenic and metastatic properties. In this review, we report on the history and recent breakthroughs in understanding TWIST protein functions and the emerging role of the associated epithelial-mesenchymal transition (EMT) in tumorigenesis. We then broaden the discussion to address the general contribution of reactivating embryonic programs in cancerogenesis.

[Role of the epithelial-mesenchymal transition during tumor progression]. / Rôle de la transition épithéliomésenchymateuse dans la progression tumorale.

The epithelial-mesenchymal transition (EMT) is a morphogenetic program that converts epithelial into mesenchymal cells during the embryonic development. This mechanism is frequently reactivated during tumor progression and provides cells with motility and invasive capabilities favoring the metastatic dissemination from epithelial tumors. Various EMT-inducing transcription factors, such as the TWIST proteins, were also shown to inhibit oncogene-induced fail-safe programs (senescence and apoptosis), thereby promoting the progression from benign to malignant stages. Altogether, these observations suggest that EMT could play an important role in favoring both tumor development and metastatic dissemination.