Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer

Purpose Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. Methods Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). Results The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months,p = 0.022). Conclusions Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. Registration number University Hospital Medical Information Network Clinical Trial Registry 000026140.

Automated summary

The study found significant differences in tryptophan metabolite levels between patients with non-small cell lung cancer and healthy volunteers, with 3-HAA levels correlating with treatment outcomes. Analysis of 3-HAA values can predict the efficacy of ICIs treatment.