• Serum glycopeptide signatures change during anti-PD-1/PD-L1 immunotherapy in advanced lung cancer patients, with 27 of 337 quantified glycopeptides showing significant alterations.
• The IgG4 glycopeptide EEQFN177STYR (H3N4) is significantly increased during treatment (FC=2.65, P=0.0083) and shows the highest increase in responders (FC=5.84, P=0.0190), suggesting a potential predictive biomarker.
• Associations between specific IgG glycopeptides (IgG4 H3N4 and IgG3 H3N4F1) and treatment response indicate their potential guiding role in cancer immunotherapy.
• The study employs mass-spectrometry-based label-free quantification and chemical labeling strategies, providing a robust workflow for glycoproteomic analysis in clinical settings.