Abstract 1072P
Background
Although immunotherapy has revolutionized the treatment of patients with non-small cell lung cancer (NSCLC), not all patients respond and reliable prognostic biomarkers are lacking. In the present study we investigated the clinical significance of mRNA expression levels of various immune checkpoints in the circulation of NSCLC patients treated with second line anti-PD1/PD-L1 therapy.
Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from 59 NSCLC patients prior to treatment with second-line immune-checkpoint inhibitors (ICIs), using ficol density gradient centrifugation and total RNA was extracted by Trizol. RT-qPCR was used to analyze mRNA expression levels of PD-1, PD-L1, IDO, LAG-3, STING and TIGIT. PGK was used as a housekeeping gene for the assessment of mRNA expression levels by 2-ΔΔCt method.
Results
Low expression levels of PD-L1, TIGIT and STING were correlated with disease progression (chi-square test, p=0.042, p=0.012 and p=0.012, respectively). In addition, low expression of PD-1, PD-L1 and TIGIT were correlated with shorter duration of disease control (PR/SD<6 months vs ≥6mo; chi-square test, p=0.009, p=0.006 and p=0.028, respectively). Low PD-L1 and TIGIT expression levels were associated with shorter progression free survival (PFS; log-rank test: p=0.042 and p=0.014, respectively) and with shorter overall survival (OS; log-rank test: p=0.044 and p=0.006, respectively) as compared to high expression. Multivariate Cox regression analysis revealed that low expression of TIGIT was an independent predictor for both shorter PFS (HR: 1.821, 95% CI: 1.069-3.102; p=0.027) and shorter OS (HR: 1.780, 95% CI: 1.004-3.156; p=0.048).
Conclusions
The assessment of expression levels of immune checkpoints in the peripheral blood may have prognostic implications in NSCLC patients treated with second-line ICIs. In addition, our results suggest that TIGIT assessed in the peripheral blood may represent promising biomarker for ICIs response beyond PD-L1.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Anticancer Research Support Association.
Disclosure
All authors have declared no conflicts of interest.