Co-blockade of immune checkpoints and adenosine A2A receptor suppresses metastasis

Arabella Young; Deepak Mittal; Kimberley Stannard; Michelle Yong; Michele Wl Teng; Bertrand Allard; John Stagg; Mark J Smyth

doi:10.4161/21624011.2014.958952

Co-blockade of immune checkpoints and adenosine A_2A receptor suppresses metastasis

Oncoimmunology. 2014 Dec 15;3(10):e958952. doi: 10.4161/21624011.2014.958952. eCollection 2014 Nov.

Authors

Arabella Young¹, Deepak Mittal¹, Kimberley Stannard², Michelle Yong², Michele Wl Teng¹, Bertrand Allard³, John Stagg³, Mark J Smyth¹

Affiliations

¹ Immunology in Cancer and Infection Laboratory and Cancer Immunoregulation and Immunotherapy Laboratories; QIMR Berghofer Medical Research Institute ; Herston, Queensland, Australia ; School of Medicine, University of Queensland ; Herston, Queensland, Australia.
² Immunology in Cancer and Infection Laboratory and Cancer Immunoregulation and Immunotherapy Laboratories; QIMR Berghofer Medical Research Institute ; Herston, Queensland, Australia.
³ Centre de Recherche du Centre Hospitalier de l'Université de Montréal; Faculté de Pharmacie et Institut du Cancer de Montréal ; Montréal, Québec, Canada.

Abstract

Immunosuppressive pathways active within the tumor microenvironment must be targeted in combination to sufficiently bolster antitumor immune defenses. Inhibition of A_2A adenosine receptor signaling in combination with immune checkpoint blockade enhances CD8⁺ T and NK cell anti-metastatic activity. This results in reduced metastatic burden and improved survival in pre-clinical models.

Keywords: PD-1; adenosine; combination therapy; immune checkpoint; metastasis; tumor-mediated immunosuppression.

Publication types

Research Support, Non-U.S. Gov't