ArticleVolume 7, Issue 1102549Open access 1Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA 2Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany 3Cancer Center Cologne Essen (CCCE), Cologne, Germany 4Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany 5University of Cologne,...
Abstract The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency.
Highlights • Exhausted CAR-T cells generate immunosuppressive adenosine through CD39/CD73 • Increased inosine metabolism induces stemness • CAR-T cells cultured in inosine-containing media have increased effector function • Inosine supplementation is a novel strategy to improve CAR-T cell manufacturing Summary Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+ CAR-T cells express CD39 and CD73, which mediate proximal steps in Ado generation.
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