Ponente
Descripción
Introduction: Lung cancer is the leading cause of death from tumors worldwide, with non-small cell lung cancer (NSCLC) being the most common histological type. Systemic therapy for metastatic NSCLC is selected based on the presence of specific biomarkers. Molecular alterations that predict response to treatment are present in only about 30% of patients with NSCLC. One of the therapeutic options for patients lacking of these mutations are PD-L1 immune checkpoint inhibitors. However, the efficacy of these therapies depends on PD-L1 expression levels in the tumor. In this work we evaluated PD-L1 levels modulation by the CK2 inhibitors, CIGB-300 peptide and CX4945 in two NSCLC cell lines.
Materials and methods: NCI-H460 and A549 cell lines were treated with 30µM and 180µM of peptide, respectively, and 5 µM CX4945 during 30 minutes, 3, 6, 24 and 48 hours. PD-L1 mRNA levels was quantified by qPCR assay and protein expression was evaluated by flow cytometry. IFN-γ was employed as positive control for PD-L1 induction.
Results: Data showed that CIGB-300 induced significant increase of PD-L1 mRNA levels after treatment during 3 and 6 hours in NCI-H460 while it was only increased at 3 hours of treatment in A549. Protein levels increased after 24 and 48 hours of treatment with the peptide in NCI-H460 cells, but not when CX4945 was using. PD-L1 protein levels were not modulated with any of the treatments evaluated in A549 cells. The results obtained suggest that CIGB-300 peptide, but not CX4945, is capable of increasing the expression of PD-L1 in cells with basal levels of this molecule.
Conclusions: All these findings could have clinical implications for the design of new therapeutic approaches of combinations of CIGB-300 with immune checkpoint inhibitors mainly in patients with NSCLC lacking actionable driver mutations.
