[A Study of Biomarkers in Immuno-Oncology - Correlation between Gut Microbiome Composition and the Effects of Immune Checkpoint Inhibitors].

ABSTRACT

Currently, anti-PD-1 inhibitors(nivolumab and pembrolizumab)are used for patients with non-small cell lung cancer (NSCLC), although the role of this biomarker is not yet fully characterized. PD-L1 expression in the tumor has been established as a biomarker of the effects of pembrolizumab; however, a number of PD-L1-negative patients have benefited from nivolumab or other immune checkpoint inhibitors, suggesting that there might be additional relevant biomarkers. Notably, tumor mutation burden or tumor infiltrating lymphocytes might be useful biomarkers for these patients; the gut microbiome has received similar attention. It has been reported that mouse models of melanoma with certain types of microbiomes benefit from the use of immune checkpoint inhibitors. Even in human cases, those with certain types of microbiomes tended to benefit from immune checkpoint inhibitor treatment and exhibited elevated CD8-positive T cell counts. Additionally, when combined with antibiotics, the effect of the anti-PD-1 antibody was attenuated; conversely, mice that were treated with certain species of bacteria experienced beneficial outcomes from anti-PD-1 antibody treatment. This suggested that manipulation of the gut microbiome might alter treatment effects. Here, we analyzed the microbiome of 12 patients with advanced or recurrent NSCLC who were treated with anti-PD-1 antibody. There was no major difference between before and after administration in microbiome of each case. Cluster analysis indicated no significant differences in oral microbiomes among the patients before the administration of the anti-PD-1 antibody. Comparative analysis of the patients' gut microbiomes is ongoing. We plan to continue further examination to reveal whether the intestinal environment influences the effectiveness of immune checkpoint inhibitors in NSCLC patients.