To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins and discover novel biomarkers related to treatment response, we analyzed a series of sera samples from patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, with mass-spectrometry-based label-free quantification methodology.