Data from: The CD73 immune checkpoint promotes tumor cell metabolic fitness

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses
anti-tumor immunity. Accordingly, several CD73 inhibitors are currently
being evaluated in the clinic, including in large randomized clinical
trials. Yet, the tumor cell-intrinsic impact of CD73 remains largely
uncharacterized. Using metabolomics, we discovered that CD73 significantly
enhances tumor cell mitochondrial respiration and aspartate biosynthesis.
Importantly, rescuing aspartate biosynthesis was sufficient to restore
proliferation of CD73-deficient tumors in immune-deficient mice. Seahorse
analysis of a large panel of mouse and human tumor cells demonstrated that
CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve.
Targeting CD73 decreased tumor cell metabolic fitness, increased genomic
instability and suppressed poly ADP ribose polymerase (PARP) activity. Our
study thus uncovered an important immune-independent function for CD73 in
promoting tumor cell metabolism and provides the rationale for previously
unforeseen combination therapies incorporating CD73 inhibition.