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Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy

Author

Listed:
  • Kimiharu Takamatsu

    (Keio University School of Medicine)

  • Nobuyuki Tanaka

    (Keio University School of Medicine)

  • Kyohei Hakozaki

    (Keio University School of Medicine)

  • Ryohei Takahashi

    (Keio University School of Medicine)

  • Yu Teranishi

    (Keio University School of Medicine)

  • Tetsushi Murakami

    (Keio University School of Medicine)

  • Ryohei Kufukihara

    (Keio University School of Medicine)

  • Naoya Niwa

    (Keio University School of Medicine)

  • Shuji Mikami

    (Keio University Hospital)

  • Toshiaki Shinojima

    (Keio University School of Medicine
    Saitama Medical University)

  • Takashi Sasaki

    (Keio University School of Medicine)

  • Yusuke Sato

    (The University of Tokyo)

  • Haruki Kume

    (The University of Tokyo)

  • Seishi Ogawa

    (Kyoto University)

  • Kazuhiro Kakimi

    (The University of Tokyo Hospital)

  • Takashi Kamatani

    (The University of Tokyo
    Tokyo Medical and Dental University (TMDU)
    Keio University School of Medicine)

  • Fuyuki Miya

    (Tokyo Medical and Dental University (TMDU))

  • Tatsuhiko Tsunoda

    (The University of Tokyo
    Tokyo Medical and Dental University (TMDU)
    RIKEN Center for Integrative Medical Sciences)

  • Eriko Aimono

    (Keio University School of Medicine)

  • Hiroshi Nishihara

    (Keio University School of Medicine)

  • Kazuaki Sawada

    (Keio University School of Medicine)

  • Takeshi Imamura

    (Ehime University
    Ehime University Hospital)

  • Ryuichi Mizuno

    (Keio University School of Medicine)

  • Mototsugu Oya

    (Keio University School of Medicine)

Abstract

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.

Suggested Citation

  • Kimiharu Takamatsu & Nobuyuki Tanaka & Kyohei Hakozaki & Ryohei Takahashi & Yu Teranishi & Tetsushi Murakami & Ryohei Kufukihara & Naoya Niwa & Shuji Mikami & Toshiaki Shinojima & Takashi Sasaki & Yus, 2021. "Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25865-0
    DOI: 10.1038/s41467-021-25865-0
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