1063P Profiling of peripheral T cell receptor beta chain repertoire in non-small cell lung cancer (NSCLC) patients treated with anti-PD1

PD-L1 expression is the most implemented biomarker in clinical practice for immunotherapy in NSCLC; however, not all patients benefit from this treatment and PD-L1 testing alone is not yet an adequate biomarker for patient selection. Consequently, new approach is necessary to identify effective biomarkers. The aim of the project is to characterize T cell receptor β chain (TCRβ) repertoire in a cohort of advanced NSCLC patients treated with anti-PD1. 15 advanced NSCLC patients treated with 1st line pembrolizumab were included. PBMCs were isolated from blood samples collected pre-treatment and at first response assessment. TCRβ libraries were prepared with Oncomine TCRβ SR (RNA) assay and sequenced on Ion GeneStudio S5 Series. To assess the contribution of TCRβ repertoire, Shannon diversity, richness, convergence, top 100 clones, and V-gene usage were tracked and evaluated in pre- and post-treatment samples for association with clinical benefit (CB) (complete or partial response, stable disease vs. progressive disease (PD)) and progression-free survival (PFS). A p-value <0.05 was considered statistically significant. More than 1 million sequencing reads were obtained per sample. Baseline data revealed a tendency to lower Shannon diversity in patients ≥60 years old compared to younger patients. Additionally, smokers showed lower richness (p=0.01) and Shannon diversity (p=0.05) when compared to non-smokers. Patients with CB displayed lower number of newly detected top 100 clones in post- treatment samples compared to patients with PD (p=0.05). TRBV11-1 was detected more in patients with CB (p=0.025), whereas TRBV7-4 was more frequent in patients with PD (p=0.003). Furthermore, patients with lower TRBV7-4 usage had improved PFS (p=0.004). Our preliminary results suggest that peripheral TCRβ repertoire might be applied to monitor the immune response in patients treated with anti-PD1. Further study in an extended cohort to validate these findings and to clarify the prognostic and/or predictive utility of the TCRβ repertoire as a biomarker in NSCLC patients will be needed. Funded by CB16-12-00350 from CIBEROnc, PI18/00226 from ISCIII, Arnal Planelles Foundation and AMACMA.