Abstract
Abstract Cancer immunotherapy has shaped the way in which we design cancer treatments, introducing the paradigm of taking advantage of our immune system to fight cancer. We propose that the same concept could be applied to infectious diseases and, especially, to those that hamper the immune system like COVID-19. It is well known that an adaptive immune response is able to eradicate viral infections and CD8+ T-cells are key in such anti-viral response. Furthermore, several studies reported that the number of CD8+ T-cells is reduced in COVID-19 patients since the beginning of SARS-CoV-2 infection and further decreased in severe cases. CD8+ T-cells often show signs of exhaustion, loss of T-cell functions and suppression in COVID-19 patients, suggesting that hampering CD8+ T-cells could be a way by which SARS-CoV-2 infection progresses. Importantly, the number of CD8+ T cells appears to re-increase in patients that are recovering from COVID-19, suggesting that CD8+ T-cells could be a key factor that determines whether our body can recover from the disease. We propose that therapies that boost CD8+ T cells could be effective in clearing SARS-CoV-2 infection in COVID-19. To test this, we will take advantage of the adenosine-mediated immunomodulation. Adenosine, an ATP metabolite that is produced during inflammation, hypoxia and in the tumor microenvironment, was found to suppress the immune response through activation of adenosine receptors present on immune cells. Small molecules antagonists that block one of these receptors, adenosine A2A receptor (A2AR) antagonists, are currently being studied to boost anti-cancer T-cell mediated immune responses. Our data show that treatment with an A2AR antagonist restores and stabilizes Notch1, a key pathway for T-cell functions, along with production of INF-gamma and Granzyme B and proliferation in CD8+ T-cells. As a proof of concept, our data indicates that treatment with an A2AR antagonist increases CD8+ T-cells anti-cancer response in tumor-derived organoids, suggesting that the treatment boosts CD8+ T-cells-mediated immune response. Ongoing work aims to test whether the A2AR antagonist treatment restores several parameters of T-cell function that are specifically modified in COVID-19. This analysis will help to predict the action of the A2AR antagonist on T-cells in vivo and we ultimately aim to test this treatment in a mouse model for COVID-19. Overall, our work could introduce a new paradigm and new therapies for COVID-19 and other infectious diseases. Citation Format: Giulia Monticone, Alistair Ramsay, Lucio Miele. Adenosine-based cancer immunotherapy for COVID-19 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P08.
Published Version
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