eLife · 8 authors, 9 centres
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This preclinical study used metabolomics, Seahorse analysis, and mouse tumor models to show that CD73, an immune checkpoint, directly enhances tumor cell mitochondrial respiration and aspartate biosynthesis in an adenosine-independent manner. The findings reveal a cell-autonomous function for CD73 in promoting tumor metabolic fitness and suggest new combination therapies.
This study investigated the tumor cell-intrinsic functions of the ectonucleotidase CD73, typically known as an immune checkpoint. Using metabolomics, Seahorse analysis on a panel of human and mouse tumor cell lines, and CD73-deficient tumor cells grown in immunodeficient mice, the authors discovered that CD73 enhances mitochondrial respiration and aspartate biosynthesis. CD73 deficiency decreased intracellular NAD+ pools, reduced PARP activity, increased genomic instability, and impaired tumor proliferation. The study was limited to preclinical models, and the mechanism of extracellular NMN accumulation was not fully elucidated.
