PUB136 Effect of PD-L1 Tumor Expression on Clinical Benefit of Personalized Dendritic Cell Based Vaccine in Patients with Non-Small Cell Lung Cancer

Abstract

Modern antitumor vaccination therapy is evidence based and one of the most promising strategies in lung cancer biotherapy today. Earlier, promising results from phase III trial of dendritic cell based vaccine immunotherapy in IIB-IIIA stage non-small cell lung cancer (NSCLC) patients have been obtained by National Cancer Institute of Ukraine. It’s known, the PD-1/PD-L1 pathway may play an important role in blunting immune response to tumor vaccines. However, the predictive value of PD-L1 tumor expression is controversial. We speculate that tumor dendritic cell (DC)-vaccine will have more benefit in NSCLC with low/- PD-L1 tumor expression. Therefore, our main goal is to examine the clinical benefit of personalized DC-vaccine therapy in NSCLC patients according to PD-L1 tumor expression. Original construction of DC-vaccine has been used: autologous DCs of monocytic origin loaded with mechanically heterogenized microparticles of tumor cells. Maturation state and functional activity of DCs were evaluated by the expression of cell surface markers CD83/86 and HLA-DR, TNF-a, IDO, TGF-b, IL-10, CCR7 and IL-12 p35/p40 mRNA level as well as bioactive IL-12p70 IL-12 protein content. DC in amount 4,62±0,37x106 per injection were injected intravenously in 1-3 courses with 6 months interval. One course consisted of 5 injections with one-month interval. Clinical and immunological monitoring of DC-vaccine immunotherapy was performed. PD-L1 gene expression level was detected in primary tumors by real-time RT-PCR. Tumors were categorized into groups according to high or low PD-L1 expression levels based on cutoff point - optimal criterion that was determined by ROC analysis (AUC=0.79, p<0.03). Sensitivity and specificity of PD-L1 gene expression as predictive biomarker for NSCLC patients received DC-vaccine therapy were 75% and 83%, respectively. Cox proportional hazard regression analysis revealed that PD-L1 gene expression level has no significant effect on 5-year overall survival (OS) rate for NSCLC patients but has a significant impact on 5-year event-free survival (EFS) of patients. Lower level of PD-L1 gene expression correlates with a significant increase in EFS (p=0.026). The 2-year EFS rate for patients with low PD-L1 gene expression was 86% compared to 29% for high expression (F-Cox criterion: F=4.68, p=0,017). PD-L1 tumor expression has a predictive significance to personalized DC-vaccine therapy. The identification of such possible predictive markers are crucial for the rational development, research and advance of combined immunotherapy and to guide the optimal choice of immunotherapy combinations schemes. Obtained results might be background for new therapy schemes which based on the anti-PD-1 inhibitor and specific immunotherapy.