Chemotherapy Immunophenoprofiles in Non-Small-Cell Lung Cancer by Personalized Membrane Proteomics

Objectives: No study has addressed how the immune status at the molecular level is affected by first-line pemetrexed and cisplatin (PEM-CIS) combination therapy in patients with non-small-cell lung cancer (NSCLC). Thus, we aimed to identify the immune status from membrane proteome alterations in patients with NSCLC upon PEM-CIS treatment. Methods: The paired peripheral blood mononuclear cells (PBMCs) were collected from four patients with lung adenocarcinoma before and after the first regimen of PEM-CIS treatment and applied quantitative membrane proteomics analysis. Result: In the personalized PBMC membrane proteome profiles, 2424 proteins were identified as displaying patient-specific responsive patterns. We discovered an elevated neutrophil activity and a more suppressive T-cell phenotype with the downregulation of cytotoxic T lymphocyte antigen 4 degradation and the upregulation of type 2 T-helper and T-regulatory cells in the patient with the highest progression-free survival (PFS) of 14.5 months. Patients with a PFS of 2 months showed higher expressions of T-cell subsets, MHC class II pathways, and T-cell receptor signaling, which indicated an activated immune status. Conclusion and Clinical Relevance: Without the additional isolation of specific immune cell populations, our study demonstrated that PEM-CIS chemotherapy altered patients' immune system in terms of neutrophils, T cells, and antigen presentation pathways.