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

Kimiharu Takamatsu, Nobuyuki Tanaka (), Kyohei Hakozaki, Ryohei Takahashi, Yu Teranishi, Tetsushi Murakami, Ryohei Kufukihara, Naoya Niwa, Shuji Mikami, Toshiaki Shinojima, Takashi Sasaki, Yusuke Sato, Haruki Kume, Seishi Ogawa, Kazuhiro Kakimi, Takashi Kamatani, Fuyuki Miya, Tatsuhiko Tsunoda, Eriko Aimono, Hiroshi Nishihara, Kazuaki Sawada, Takeshi Imamura, Ryuichi Mizuno and Mototsugu Oya
Additional contact information
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
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
Fuyuki Miya: Tokyo Medical and Dental University (TMDU)
Tatsuhiko Tsunoda: The University of Tokyo
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
Ryuichi Mizuno: Keio University School of Medicine
Mototsugu Oya: Keio University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25865-0

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DOI: 10.1038/s41467-021-25865-0

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