Shotgun proteomic profiling of serum from patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint blockade (ICB) monotherapy. Top-14 abundant proteins were depleted (Pierce High-Select, Thermo Fisher Scientific), and tryptic digests were spiked with the Pierce Peptide Retention Time Calibration Mixture as an internal standard. Peptides were analyzed by LC-MS/MS on an EASY-nLC 1200 coupled to an Orbitrap Eclipse Tribrid mass spectrometer with a FAIMS Pro interface (compensation voltages −40, −60, −80 V), using data-dependent acquisition with Orbitrap MS1 and ion-trap-detected HCD MS2. Raw files were searched in Proteome Discoverer 2.4 (SEQUEST HT with Percolator validation) against UniProt Swiss-Prot human (release 2017-10-25), and label-free protein abundances (Minora Feature Detector) were normalized to internal standard peptides. See the associated publication for full experimental details and clinical information.