Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor

Mittal, Deepak, Young, Arabella, Stannard, Kimberley, Yong, Michelle, Teng, Michele W. L., Allard, Bertrand, Stagg, John and Smyth, Mark J. (2014) Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor. Cancer Research, 74 14: 3652-3658. doi:10.1158/0008-5472.CAN-14-0957


Author Mittal, Deepak
Young, Arabella
Stannard, Kimberley
Yong, Michelle
Teng, Michele W. L.
Allard, Bertrand
Stagg, John
Smyth, Mark J.
Title Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
0008-5472
Publication date 2014-07-15
Year available 2014
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-14-0957
Volume 74
Issue 14
Start page 3652
End page 3658
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe clinical profile of adenosine A2A receptor inhibitors (A2ARi) in Parkinson disease. Metastasis is the main cause of cancer-related deaths worldwide, and therefore we have studied experimental and spontaneous mouse models of melanoma and breast cancer metastasis to demonstrate the efficacy and mechanism of a combination of A2ARi in combination with anti-PD-1 monoclonal antibody (mAb). This combination significantly reduces metastatic burden and prolongs the life of mice compared with either monotherapy alone. Importantly, the combination was only effective when the tumor expressed high levels of CD73, suggesting a tumor biomarker that at a minimum could be used to stratify patients that might receive this combination. The mechanism of the combination therapy was critically dependent on NK cells and IFNγ, and to a lesser extent, CD8+ T cells and the effector molecule, perforin. Overall, these results provide a strong rationale to use A2ARi with anti-PD-1 mAb for the treatment of minimal residual and metastatic disease.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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