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CD38-mediated acquired resistance to PD-1/PD-L1 Inhibitors. Malignant cells resistant to checkpoint inhibition produce mediators such as ATR that lead to CD38 up-regulation via RARα. CD38 catalyzes the conversion of NAD+ into immunosuppressive adenosine via the CD38/CD203a/CD73 ectoenzymatic pathway. Adenosine interacts with A2AR and A2BR adenosine receptors on CD8+ T cells, thus suppressing cytotoxic activity.
