Abstract 1250P
Background
Immune checkpoint inhibitors in cancer therapy have improved clinical responses and overall survival for patients with non-small cell lung cancer (NSCLC). However, the response is not equal and known NSCLC biomarkers are not sufficient in predicting the therapy outcome. Plasma proteins in NSCLC patients treated with anti-PD-1-blockade were investigated using a high-throughput data independent acquisition mass spectrometry (DIA-MS).
Methods
Samples were analyzed by capillary flow liquid chromatography coupled to DIA-MS. Data were extracted with SpectronautTM to quantify proteins. Multiple statistical approaches were used to identify significantly changing proteins across conditions (baseline/after treatment, responder/non-responder) and select a panel of protein biomarker candidates.
Results
125 plasma samples from late stage NSCLC patients treated with immunotherapy regimens - 75 baseline and 50 after 8-weeks treatment-were analyzed and more than 580 proteins were quantified. Panels of proteins significantly changing between responder and non-responder at baseline, treatment and across both timepoints were identified. Identified proteins were involved in various immune responses (e.g. platelet aggregation), glycolysis, cell adhesion and inflammation (e.g. ALDOA, VCL, LBP). In addition, several proteins with known association to different types of cancer (e.g. CRTAC1, C9, LRG1) were found. Data were also correlated with orthogonal assays (flow cytometry). All above allowed the separation of subjects according to the responder status.
Conclusions
Proteomic profiling of plasma samples using DIA-MS enables a holistic analysis of potential circulating biomarkers. Comparison of protein signatures across study duration can provide a detailed roadmap of processes governing successful treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Biognosys AG.
Funding
Biognosys AG.
Disclosure
E. Romano: Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche/Genentech; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: AstraZeneca/MedImmune; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Roche. V. Dozio: Full/Part-time employment: Biognosys AG. K. Sklodowski: Full/Part-time employment: Biognosys AG. All other authors have declared no conflicts of interest.