Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses

Arabella Young, Shin Foong Ngiow, Deborah S. Barkauskas, Erin Sult, Carl Hay, Stephen J. Blake, Qihui Huang, Jing Liu, Kazuyoshi Takeda, Michele W.L. Teng, Kris Sachsenmeier, Mark J. Smyth

Research output: Contribution to journalArticlepeer-review

291 Citations (Scopus)

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 languageEnglish
Pages (from-to)391-403
Number of pages13
JournalCancer Cell
Volume30
Issue number3
DOIs
Publication statusPublished or Issued - 12 Sept 2016
Externally publishedYes

Keywords

  • CD73
  • adenosine
  • combination therapy
  • immunotherapy
  • tumor

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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