Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses
Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes suggérant l'intérêt de développer des thérapies ciblées sur CD73 et A2AR pour augmenter la réponse antitumorale du système immunitaire
Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-?, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors. In a two-way mixed leukocyte reaction using a fully human anti-CD73, we demonstrated that Fc receptor binding augmented the production of proinflammatory cytokines.
Cancer Cell 2016