A novel bioassay reflecting response to immune checkpoint inhibitor therapy in non-small cell lung cancer with malignant pleural effusion.

BACKGROUND

Immune checkpoint inhibitor (ICI) therapy has prolonged the survival of a proportion of patients with advanced non-small cell lung cancer (NSCLC). Histological quantification of programmed cell death-ligand 1 (PD-L1) in tumors is a widely adopted marker for predicting the efficacy of ICI treatment. However, its use in patients with malignant pleural effusion (MPE) is occasionally challenging because of the difficulty of tissue sampling. The aim of this study was to identify new predictive factors for ICI treatment in patients with MPE.

METHODS

A total of 22 patients with MPE were included. Initially, we surveyed several parameters of pleural effusion in relation to overall survival (OS). Next, we attempted to reflect the response to ICI treatment , a simple co-culture bioassay was designed, in which tumor cells and immune cells were co-cultured with nivolumab. Binding of nivolumab to T cells was confirmed by flow cytometry, and the released interferon-gamma (IFN-γ) was evaluated by enzyme-linked immunosorbent assay.

RESULTS

The parameter analysis demonstrated that the levels of albumin and the percentage of lymphocyte were significantly correlated with OS in all patients. Vascular endothelial growth factor (VEGF) and high mobility group box 1 (HMGB1) were negatively correlated with OS in only driver gene mutation-positive patients. bioassay showed that nivolumab-binding T cells predominantly produced IFN-γ compared with control antibody. Of the 22 patients, 12 showed an increase in IFN-γ release after treatment with nivolumab. Despite the lack of significant correlations between IFN-γ levels and OS, the duration of ICI treatment tended to be longer in patients with IFN-γ release versus those without IFN-γ release.

CONCLUSIONS

This immune assay of IFN-γ release after treatment with nivolumab may identify responders prior to ICI treatment.