Targeting the adenosine immune checkpoint for cancer therapy

John Stagg, PhD
Lab Head
Université de Montréal Hospital Research Centre (CRCHUM)

Professor
Faculty of Pharmacy
Université de Montréal

This conference is hosted by Javier M. Di Noia, PhD . This conference is part of the 2023-2024 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

Online:
Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

About this conference
Extracellular adenosine (eADO) is a multifunctional metabolite that accumulates from the breakdown of extracellular ATP by the ecto-nucleotidases CD39 and CD73. Signaling through the A2A adenosine receptor inhibits local and systemic inflammation and promotes tissue repair. In the inflamed and hypoxic tumor microenvironment (TME), A2A-driven immunosuppression promotes tumor development. In the first part of my talk, I will discuss our recent and unexpected findings that the anti-obesogenic and anti-inflammatory functions of A2A are important to restrain hepatocellular carcinoma (HCC) development. Conditional A2A deletion revealed critical roles of myeloid and hepatocyte-derived A2A signaling in restraining HCC by limiting hepatic inflammation and steatosis. Our study importantly uncovers a previously unappreciated tumor suppressive function for A2A in the context of liver diseases such as Nonalcoholic Steatohepatitis (NASH), and therefore suggests caution in the use of A2A antagonists in cancer patients. In the second part of my talk, I will discuss on-going work on a new therapeutic target of the adenosine signaling pathway. Our work demonstrates for the first time that pharmacological inhibition of this target synergizes with anti-PD-1 therapy in preclinical cancer models.

About John Stagg
Dr. John Stagg is a researcher at the CHUM Research Centre and Professor of Pharmacy at Université de Montréal. Distinguished immunologist, Dr. Stagg is recognized for having identified the adenosine-producing enzyme CD73 as a new cancer target. With over 100 peer-reviewed publications, Dr. Stagg demonstrated that blocking adenosine production stimulates anti-tumor immunity and synergizes with immune checkpoint inhibitors. Largely as a result of Dr. Stagg’s work, over 30 clinical trials have been registered to evaluate an adenosine-targeting agent in immuno-oncology, including a randomized phase 3 clinical trial in patients with stage 3 lung cancer. Dr. Stagg is part of the Translational Advisory Committee (TAC) of several clinical trials immuno-oncology, a member of the Scientific Advisory Board of Domain Therapeutics, Surface Oncology, and Tarus Therapeutics, and Board member of BioCanRx. Dr. Stagg’s work is funded by the CIHR, the Canadian Cancer Society, Ovarian Cancer Canada and MITACS.

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