Multiprong CD38 targeting to enhance anti-PD1 immune checkpoint blockade efficacy.

CD38, a multifunctional enzyme involved in NAD+ catabolism, is hypothesized to act as a metabolic checkpoint for antitumor CD8 T cells. A recent study discovered that, apart from its direct metabolic mechanisms, CD38-mediated RyR2-AKT-TCF1 signaling regulates responsiveness to anti-PD1 cancer therapy at the molecular level. These findings advocate multiprong CD38 targeting to overcome resistance to immune checkpoint blockade therapy.