Prior studies in patients with CIADM suggest potential risk factors for development of CIADM, but these studies have been limited. Genetic risk factors include a higher prevalence of HLA-DR4 and a germline mutation in NLRC5, a key class I transcription activator, in patients with CIADM. Elevated pancreatic enzymes close to the time of CIADM diagnosis and reduced pancreatic volumes at the time of CIADM have been reported, consistent with pancreatic inflammation. In rare cases in which human pancreatic tissue is available, lymphocytic infiltrate and inflammatory cytokines have been reported. In this issue, Wu et al. (16) identified biomarkers in the periphery and changes in the pancreas at baseline (prior to ICI treatment) in patients who later developed CIADM compared with patients who did not. These included an increased frequency of detectable anti-GAD and anti-insulin antibodies, changes in immune cells by flow cytometry consistent with immune activation, and reduced pancreatic volume. Together, these baseline differences were predictive of the development of CIADM. Furthermore, Wu et al. identified elevated cytokine levels (IFN-γ, TNF-α, IL-2, IL-4) at the time of CIADM diagnosis that contribute to our understanding of the mechanisms underlying this complication. The figure summarizes the findings of Wu et al. as well as prior studies, as indicated by citation.