Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17631
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Karayama Masato 浜松医科大学, 医学部附属病院, 講師 (90748071)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: トリプトファン

Outline of Final Research Achievements

Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small-cell lung cancer (NSCLC).
The 19 patients with NSCLC had significantly lower levels of tryptophan (p=0.002) and xanthurenic acid (p=0.032), and 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 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%, 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.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

従来の標準的なバイオマーカーであるPD-L1発現を補うことができるバイオマーカーであり、末梢血を用いた検査であるため低侵襲で繰り返し検査することが可能である。また、ICIの治療適応となるその他のがん種にも応用が期待される。