A mouse pancreatic organoid model to compare PD-L1 blocking antibodies

Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape for cancer patients, but diabetes, a rare, severe immune-related endocrinopathy, is linked to ICI therapy. It is unclear whether glycosylation of ICIs may play a role in the development of this adverse event and how the physiological effects of different ICIs on pancreatic cells should be evaluated. We used a mouse pancreatic organoid model to compare three PD-L1 blocking antibodies in the presence or absence of IFN gamma using a metabolic bioanalyzer. Modulation of ICI glycosylation altered its metabolic effects on mouse pancreatic organoids, suggesting that this model could be used to monitor and compare ICIs and to study the mechanisms underlying the development of IC-mediated diabetes.

Automated summary

ICIs have revolutionized the treatment of cancer patients, but a rare and severe immune-related endocrinopathy called diabetes is associated with this therapy. This study investigated the role of glycosylation in the development of IC-mediated diabetes and the evaluation of different ICIs' physiological effects on pancreatic cells using a mouse pancreatic organoid model. The findings suggest that modulation of ICI glycosylation can alter their metabolic effects on pancreatic cells, and this model can be used for monitoring and comparing ICIs, as well as studying the underlying mechanisms of IC-mediated diabetes.