Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers

Keisuke Kataoka, Yuichi Shiraishi, Yohei Takeda, Seiji Sakata, Misako Matsumoto, Seiji Nagano, Takuya Maeda, Yasunobu Nagata, Akira Kitanaka, Seiya Mizuno, Hiroko Tanaka, Kenichi Chiba, Satoshi Ito, Yosaku Watatani, Nobuyuki Kakiuchi, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Masashi Sanada, Hidehiro Itonaga, Yoshitaka Imaizumi, Yasushi Totoki, Wataru Munakata, Hiromi Nakamura, Natsuko Hama, Kotaro Shide, Yoko Kubuki, Tomonori Hidaka, Takuro Kameda, Kyoko Masuda, Nagahiro Minato, Koichi Kashiwase, Koji Izutsu, Akifumi Takaori-Kondo, Yasushi Miyazaki, Satoru Takahashi, Tatsuhiro Shibata, Hiroshi Kawamoto, Yoshiki Akatsuka, Kazuya Shimoda, Kengo Takeuchi, Tsukasa Seya, Satoru Miyano and Seishi Ogawa ()
Additional contact information
Keisuke Kataoka: Graduate School of Medicine, Kyoto University
Yuichi Shiraishi: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo
Yohei Takeda: Graduate School of Medicine, Hokkaido University
Seiji Sakata: Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research
Misako Matsumoto: Graduate School of Medicine, Hokkaido University
Seiji Nagano: Institute for Frontier Medical Science, Kyoto University
Takuya Maeda: Institute for Frontier Medical Science, Kyoto University
Yasunobu Nagata: Graduate School of Medicine, Kyoto University
Akira Kitanaka: Faculty of Medicine, University of Miyazaki
Seiya Mizuno: Laboratory Animal Resource Center and Faculty of Medicine, University of Tsukuba
Hiroko Tanaka: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo
Kenichi Chiba: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo
Satoshi Ito: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo
Yosaku Watatani: Graduate School of Medicine, Kyoto University
Nobuyuki Kakiuchi: Graduate School of Medicine, Kyoto University
Hiromichi Suzuki: Graduate School of Medicine, Kyoto University
Tetsuichi Yoshizato: Graduate School of Medicine, Kyoto University
Kenichi Yoshida: Graduate School of Medicine, Kyoto University
Masashi Sanada: Clinical Research Center, Nagoya Medical Center
Hidehiro Itonaga: Sasebo City General Hospital
Yoshitaka Imaizumi: Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University
Yasushi Totoki: National Cancer Center Research Institute
Wataru Munakata: National Cancer Center Hospital
Hiromi Nakamura: National Cancer Center Research Institute
Natsuko Hama: National Cancer Center Research Institute
Kotaro Shide: Faculty of Medicine, University of Miyazaki
Yoko Kubuki: Faculty of Medicine, University of Miyazaki
Tomonori Hidaka: Faculty of Medicine, University of Miyazaki
Takuro Kameda: Faculty of Medicine, University of Miyazaki
Kyoko Masuda: Institute for Frontier Medical Science, Kyoto University
Nagahiro Minato: Graduate School of Medicine, Kyoto University
Koichi Kashiwase: Japanese Red Cross Kanto-Koshinetsu Block Blood Center
Koji Izutsu: Toranomon Hospital
Akifumi Takaori-Kondo: Graduate School of Medicine, Kyoto University
Yasushi Miyazaki: Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University
Satoru Takahashi: Laboratory Animal Resource Center and Faculty of Medicine, University of Tsukuba
Tatsuhiro Shibata: National Cancer Center Research Institute
Hiroshi Kawamoto: Institute for Frontier Medical Science, Kyoto University
Yoshiki Akatsuka: Fujita Health University School of Medicine
Kazuya Shimoda: Faculty of Medicine, University of Miyazaki
Kengo Takeuchi: Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research
Tsukasa Seya: Graduate School of Medicine, Hokkaido University
Satoru Miyano: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo
Seishi Ogawa: Graduate School of Medicine, Kyoto University

Nature, 2016, vol. 534, issue 7607, 402-406

Abstract: Structural variations disrupting the 3′ region of PD-L1 are shown to aid immune evasion in a number of human cancers, including adult T-cell leukaemia/lymphoma, and in a mouse tumour model, CRISPR/Cas9-mediated deletion of the 3'-UTR of Pd-l1 is also shown to result in immune escape, suggesting that PD-L1 3′-UTR disruption could provide a diagnostic marker to identify patients who will benefit from anti-PD-1/PD-L1 therapy.

Date: 2016
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DOI: 10.1038/nature18294

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