Proteomic and Metabolomic Profiling of Plasma Predict Immune-related Adverse Events in Older Patients with Advanced Non-small Cell Lung Cancer

The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography–tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, B cell, and higher IL-10 and CCL2 levels at baseline. Besides, lower ALDOB, higher ST6GAL1 and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with Grade 2-4 irAEs from Grade 0-1 (AUC=0.831) and to distinguish patients with Grade 3-4 irAEs from Grade 2 (AUC=1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.