Abstract
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-γ, 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.
Original language | English |
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Pages (from-to) | 391-403 |
Number of pages | 13 |
Journal | Cancer Cell |
Volume | 30 |
Issue number | 3 |
DOIs | |
Publication status | Published or Issued - 12 Sept 2016 |
Externally published | Yes |
Keywords
- CD73
- adenosine
- combination therapy
- immunotherapy
- tumor
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research