Abstract
PurposeTryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity.MethodsPlasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC).ResultsThe 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).ConclusionsTryptophan metabolites may have a potential for predicting the efficacy of ICIs.Registration numberUniversity Hospital Medical Information Network Clinical Trial Registry 000026140.
Highlights
Immune checkpoint inhibitors (ICIs) is increasingly used for a wide variety of cancers [1]
The median progression-free survival (PFS) was 7.0 months [95% confident interval (CI): 1.6 months – not estimated], and the median OS was 12.4 months
Quantitation of 3-hydroxyanthranilic acid (3-HAA) had a high accuracy for the prediction of ICI efficacy, which was further increased when combined with PD-L1 expression
Summary
Immune checkpoint inhibitors (ICIs) is increasingly used for a wide variety of cancers [1]. ICIs are not effective for all patients. Developing new biomarkers that can accurately select patients who will benefit from ICIs is strongly desired. Tryptophan is an essential amino acid, and its metabolites are known to be bioactive compounds that play important roles in several chronic diseases and cancers [3, 4]. Tryptophan metabolites are broadly divided into three major pathways: the serotonin, indole-3-acetic acid, and kynurenine pathways. The majority of free tryptophan is catalyzed by indoleamine-2,3-dioxygenase (IDO) into kynurenine, which is the first and rate-limiting step of the catabolic tryptophan–kynurenine pathway (Supplementary Figure). The tryptophan–kynurenine pathway plays a key role in cancer
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