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

Research Project

Project/Area Number 19K17631
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionHamamatsu 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
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsトリプトファン / がん免疫 / 腫瘍微小環境 / 免疫チェックポイント阻害剤 / PD-1 / PD-L1 / 肺がん / バイオマーカー / トリプトファン代謝物
Outline of Research at the Start

免疫チェックポイント阻害剤を投与する肺がん患者に対し、治療前後で末梢血採血を行い、LC/MS分析で、トリプトファン代謝物を網羅的に測定する。測定したトリプトファン代謝物と免疫チェックポイント阻害剤の奏効率、無増悪生存期間、全生存期間の関連を解析する。この他、腫瘍の病理組織を用いて、腫瘍のPD-L1、PD-L2、IDO-1発現、腫瘍浸潤性リンパ球の評価、NGSによるTMBの解析、末梢血単核球分画を用いたCD4/8陽性T細胞、制御性T細胞の測定を行い、トリプトファン代謝産物との関連を調べ、各種バイオマーカーを用いて効果予測に最適な項目の組み合わせを探索する。

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.

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。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (1 results)

All 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer2020

    • Author(s)
      Karayama M.、Masuda J.、Mori K.、Yasui H.、Hozumi H.、Suzuki Y.、Furuhashi K.、Fujisawa T.、Enomoto N.、Nakamura Y.、Inui N.、Suda T.、Maekawa M.、Sugimura H.、Takada A.
    • Journal Title

      Clinical and Translational Oncology

      Volume: 23 Issue: 2 Pages: 418-423

    • DOI

      10.1007/s12094-020-02421-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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