Updated on 2021/10/05

写真a

 
NISHIKAWA Hiroyoshi
 
Organization
Graduate School of Medicine Program in Integrated Medicine Microbiology and Immunology Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Professor

Degree 1

  1. 博士(医学) ( 2002.3   三重大学 ) 

Research Interests 4

  1. 免疫監視

  2. 免疫寛容

  3. 腫瘍免疫

  4. 免疫学

Research Areas 3

  1. Life Science / Immunology

  2. Life Science / Tumor biology

  3. Life Science / Tumor diagnostics and therapeutics

Research History 12

  1. Nagoya University

    2020.4

  2. Nagoya University   Institute for Advanced Research

    2018.4 - 2020.4

  3. 名古屋大学大学院医学系研究科 微生物・免疫学講座 分子細胞免疫学   教授 (クロスアポイントメント)

    2016.4

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    Country:Japan

  4. 国立がん研究センター   研究所 腫瘍免疫研究分野/先端医療開発センター 免疫TR分野   分野長

    2015.4

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    Country:Japan

  5. Roswell Park Cancer Institute   Department of Oncology   Adjunctive Associate Professor (Concurrent post)

    2012.2 - 2015.3

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    Country:United States

  6. Osaka University   Designated associate professor

    2010.4 - 2015.3

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    Country:Japan

  7. 三重大学大学院医学系研究科   病態解明医学講座   講師

    2006.9 - 2010.3

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    Country:Japan

  8. Memorial Sloan Kettering Cancer Center   Research fellow

    2003.9 - 2006.8

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    Country:United States

  9. 三重大学医学部附属病院   血液・腫瘍内科   医員

    2002.4 - 2003.8

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    Country:Japan

  10. 鈴鹿中央総合病院   内科   医員

    1997.4 - 1998.3

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    Country:Japan

  11. 松阪中央総合病院   研修医

    1995.10 - 1997.3

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    Country:Japan

  12. 三重大学医学部附属病院   研修医

    1995.5 - 1995.9

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    Country:Japan

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Education 2

  1. Mie University   Graduate School, Division of Medical Sciences

    1998.4 - 2002.3

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    Country: Japan

  2. Mie University   Faculty of Medicine

    1989.4 - 1995.3

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    Country: Japan

Professional Memberships 6

  1. 日本癌学会   会員、評議員

    2013.4

  2. 日本免疫学会   会員、評議員

    2012.4

  3. 日本がん免疫学会   会員、評議員、理事

    2009.4

  4. American Society of Clinical Oncology   Full member

  5. Society for Immunotherapy of Cancer   Active member

  6. American Association for Cancer Research   Active member

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Awards 8

  1. Highly cited researcher-2020 (Web of Science)

    2020.11   Clarivate Analytics  

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    Country:United States

  2. SITC ( Society for Immunotherapy of Cancer ) Team Science Award

    2020.11   SITC  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  3. AAAS (American Association for the Advancement of Science) elected fellow 2020

    2020.10   AAAS  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  4. JCA-Mauvernay Award

    2017.9   Immune suppressive mechanisms as a target of effective cancer immunotherapy

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  5. Cancer Research Institute, CLIP Award

    2013.6   Cancer Research Institute  

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:United States

  6. Cancer Research Institute, Investigator Award

    2008.6   Cancer Research Institute  

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:United States

  7. 日本癌学会奨励賞

    2006.10   日本癌学会   腫瘍由来自己抗原を用いた癌ワクチン療法の開発

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    Award type:International academic award (Japan or overseas)  Country:Japan

  8. 三医会賞

    2003.6   三医会  

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    Country:Japan

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Papers 68

  1. Antitumour immunity regulated by aberrant ERBB family signalling Reviewed

    Kumagai S, Koyama S, Nishikawa H

    Nat Rev Cancer.   Vol. 21 ( 3 ) page: 181 - 197   2021.3

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41568-020-00322-0

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  2. Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer Reviewed

    JCI insight   Vol. 6 ( 9 ) page: Onlineahead of print   2021.5

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  3. Transcriptional regulatory network for the establishment of CD8(+) T cell exhaustion Reviewed

      Vol. 53 ( 2 ) page: 202 - 209   2021.2

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    Authorship:Last author, Corresponding author  

    DOI: 10.1038/s12276-021-00568-0

    Web of Science

  4. Newly emerged immunogenic neoantigens in established tumors enable hosts to regain immunosurveillance in a T-cell-dependent manner Reviewed

    Muramatsu T, Noguchi T, Sugiyama D, Kanada Y, Fujimaki K, Ito S, Gotoh M, Nishikawa H

    Int Immunol.   Vol. 33 ( 1 ) page: 39 - 48   2021.1

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxaa049

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  5. Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants Reviewed

    Arakawa, A; Ichikawa, H; Kubo, T; Motoi, N; Kumamoto, T; Nakajima, M; Yonemori, K; Noguchi, E; Sunami, K; Shiraishi, K; Kakishima, H; Yoshida, H; Hishiki, T; Kawakubo, N; Kuroda, T; Kiyokawa, T; Yamada, K; Yanaihara, N; Takahashi, K; Okamoto, A; Hirabayashi, S; Hasegawa, D; Manabe, A; Ono, K; Matsuoka, M; Arai, Y; Togashi, Y; Shibata, T; Nishikawa, H; Aoki, K; Yamamoto, N; Kohno, T; Ogawa, C

    NEW ENGLAND JOURNAL OF MEDICINE     page: 42 - 50   2021.1

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  6. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies Reviewed

    Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakaumra H, Takeuchi Y, Kochin, V, Itahashi K, Maeda Y, Matsui S, Shibahara,T, Yamashita Y, Irie T, Tsuge A, Fukuoka S, Kawazoe A, Udagawa H, Kirita K, Aokage K, Ishii G, Kuwata T, Nakama K, Kawazu M, Ueno T, Yamazaki N, Goto K, Tsuboi M, Mano H, Doi T, Shitara K, Nishikawa H

    Nat Immunol.   Vol. 21 ( 11 ) page: 1346 - +   2020.11

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41590-020-0769-3

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  7. The critical role of CD4(+) T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma Reviewed

    Nagasaki, J; Togashi, Y; Sugawara, T; Itami, M; Yamauchi, N; Yuda, J; Sugano, M; Ohara, Y; Minami, Y; Nakamae, H; Hino, M; Takeuchi, M; Nishikawa, H

    BLOOD ADVANCES     page: 4069 - 4082   2020.9

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    Authorship:Last author, Corresponding author  

    DOI: 10.1182/bloodadvances.2020002098

  8. An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells Reviewed

    Kumagai S, Togashi Y, Sakai C, Kawazoe A, Kawazu M, Ueno T, Sato E, Kuwata T, Kinoshita T, Yamamoto M, Nomura S, Tsukamoto T, Mano H, Shitara K, Nishikawa H

    Immunity.   Vol. 53 ( 1 ) page: 187 - +   2020.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.immuni.2020.06.016

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  9. The potential application of PD-1 blockade therapy for early-stage biliary tract cancer Reviewed

    Umemoto, Kumiko; Togashi, Yosuke; Arai, Yasuhito; Nakamura, Hiromi; Takahashi, Shinichiro; Tanegashima, Tokiyoshi; Kato, Mikiya; Nishikawa, Tsubasa; Sugiyama, Daisuke; Kojima, Motohiro; Gotohda, Naoto; Kuwata, Takeshi; Ikeda, Masafumi; Shibata, Tatsuhiro; Nishikawa, Hiroyoshi

    INTERNATIONAL IMMUNOLOGY     page: 273 - 281   2020.4

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    Authorship:Last author, Corresponding author  

    DOI: 10.1093/intimm/dxz080

  10. Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells Reviewed

    Tanaka, A; Nishikawa, H; Noguchi, S; Sugiyama, D; Morikawa, H; Takeuchi, Y; Ha, D; Shigeta, N; Kitawaki, T; Maeda, Y; Saito, T; Shinohara, Y; Kameoka, Y; Iwaisako, K; Monma, F; Ohishi, K; Karbach, J; Jager, E; Sawada, K; Katayama, N; Takahashi, N; Sakaguchi, S

    JOURNAL OF EXPERIMENTAL MEDICINE     2020.2

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    Authorship:Lead author  

    DOI: 10.1084/jem.20191009

  11. Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer Reviewed

    Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H.

    Sci Immunol.   Vol. 5 ( 43 ) page: pii: eaav3937   2020.1

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/sciimmunol.aav3937

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  12. Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids. Reviewed

    Tokunaga A, Sugiyama D, Maeda Y, Warner AB, Panageas KS, Ito S, Togashi Y, Sakai C, Wolchok JD, Nishikawa H

    J Exp Med.   Vol. 216 ( 12 ) page: 2701-2713   2019.12

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20190738

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  13. Immune Suppression by PD-L2 against Spontaneous and Treatment-Related Antitumor Immunity. Reviewed

    Tanegashima T, Togashi Y, Azuma K, Kawahara A, Ideguchi K, Sugiyama D, Kinoshita F, Akiba J, Kashiwagi E, Takeuchi A, Irie T, Tatsugami K, Hoshino T, Eto M, Nishikawa H.

    Clin Cancer Res.   Vol. 25 ( 15 ) page: 4808-4819   2019.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1158/1078-0432.CCR-18-3991

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  14. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target? Reviewed

    Ohue Y, Nishikawa H

    Cancer Sci.   Vol. 110 ( 7 ) page: 2080-2089   2019.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.14069

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  15. Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Reviewed

    Togashi Y, Shitara K, Nishikawa H

    Nat Rev Clin Oncol.   Vol. 16 ( 6 ) page: 356-371   2019.6

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41571-019-0175-7

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  16. PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Reviewed

    Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, Sato E, Fukuoka S, Tada Y, Tanaka A, Morikawa H, Kawazoe A, Kinoshita T, Shitara K, Sakaguchi S, Nishikawa H.

    Proc Natl Acad Sci U S A.   Vol. 116 ( 20 ) page: 9999-10008   2019.5

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.1822001116

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  17. Meddling with meddlers: curbing regulatory T cells and augmenting antitumor immunity. Reviewed

    Kochin V, Nishikawa H

    Nagoya J Med Sci.   Vol. 81 ( 1 ) page: 1-18   2019.2

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.18999/nagjms.81.1.1

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  18. Targeting VEGFR2 with Ramucirumab strongly impacts effector/ activated regulatory T cells and CD8+ T cells in the tumor microenvironment. Reviewed

    Tada Y, Togashi Y, Kotani D, Kuwata T, Sato E, Kawazoe A, Doi T, Wada H, Nishikawa H, Shitara K.

    J Immunother Cancer.   Vol. 6 ( 1 ) page: 106   2018.10

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    DOI: 10.1186/s40425-018-0403-1

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  19. Regulatory T cells: a potential target in cancer immunotherapy. Reviewed

    Shitara K, Nishikawa H

    Ann N Y Acad Sci.   Vol. 1417 ( 1 ) page: 104-115   2018.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/nyas.13625

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  20. Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma. Reviewed

    Takeuchi Y, Tanemura A, Tada Y, Katayama I, Kumanogoh A, Nishikawa H

    Int Immunol.   Vol. 30 ( 1 ) page: 13-22   2018.2

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxx073

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  21. Suppression from beyond the grave Reviewed

    Togashi Y, Nishikawa H

    Nat Immunol.   Vol. 18 ( 12 ) page: 1285-1286   2017.11

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    DOI: 10.1038/ni.3870

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  22. Roles of regulatory T cells in cancer immunity. Invited Reviewed

    Takeuchi Y, Nishikawa H.

    Int Immunol.   Vol. 8   page: 401-409   2016.8

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    DOI: 10.1093/intimm/dxw025.

  23. Two FOXP3+CD4+ T-cell subpopulations distinctly control the prognosis of colorectal cancers. Reviewed

    Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, Maeda Y, Hamaguchi M, Ohkura N, Sato E, Nagase H, Nishimura J, Yamamoto H, Takiguchi S, Tanoue T, Suda W, Morita H, Hattori M, Honda K, Mori M, Doki Y and Sakaguchi S.

    Nat Med.   Vol. 22 ( 6 ) page: 679-684   2016.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm.4086.

  24. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Reviewed

    Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S.

    Science   Vol. 346 ( 6216 ) page: 1536-1540   2014.12

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/science.aaa1292.

  25. Regulatory T cells in cancer immunotherapy. Invited Reviewed

    Nishikawa H, Sakaguchi S.

    Curr Opin Immunol.     2014.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.coi.2013.12.005.

  26. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Reviewed

    Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jäger E, Sakaguchi S

    Proc Natl Acad Sci U S A.   Vol. 110 ( 44 ) page: 17945-17950   2013.10

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.1316796110.

  27. Intracellular tumor-associated antigens represent effective targets for passive immunotherapy. Reviewed

    Noguchi T, Kato T, Wang L, Maeda Y, Ikeda H, Sato E, Knuth A, Gnjatic S, Ritter G, Sakaguchi S, Old LJ, Shiku H, Nishikawa H.

    Cancer Res.   Vol. 72 ( 7 ) page: 1672-1682   2012.4

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    Authorship:Lead author, Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1158/0008-5472.CAN-11-3072.

  28. Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. Reviewed

    Nishikawa H, Maeda Y, Ishida T, Gnjatic S, Sato E, Mori F, Sugiyama D, Ito A, Fukumori Y, Utsunomiya A, Inagaki H, Old LJ, Ueda R, Sakaguchi S.

    Blood   Vol. 119 ( 13 ) page: 3097-3104   2012.3

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2011-09-379982.

  29. TAS-116 plus nivolumab in patients with colorectal cancer and other solid tumors: an, open-label, dose-finding, and expansion phase Ib trial (EPOC1704).

    Kawazoe A, Itahashi K, Yamamoto N, Kotani D, Kuboki Y, Taniguchi H, Harano K, Naito Y, Suzuki M, Fukutani M, Shima H, Higuchi T, Ikeno T, Wakabayashi M, Sato A, Koyama S, Nishikawa H, Shitara K

    Clinical cancer research : an official journal of the American Association for Cancer Research     2021.9

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    DOI: 10.1158/1078-0432.CCR-21-1929

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  30. Engineering strategies for broad application of TCR-T and CAR-T cell therapies.

    Watanabe K, Nishikawa H

    International immunology     2021.8

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    DOI: 10.1093/intimm/dxab052

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  31. Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP(+) regulatory T cells

    Satoh Kazuki, Kobayashi Yoichi, Fujimaki Kaori, Hayashi Shinko, Ishida Saori, Sugiyama Daisuke, Sato Takahiko, Lim Kyungtaek, Miyamoto Megumi, Kozuma Shiho, Kadokura Michinori, Wakita Kenichi, Hata Masato, Hirahara Kazuki, Amano Masato, Watanabe Ichiro, Okamoto Atsushi, Tuettenberg Andrea, Jonuleit Helmut, Tanemura Atsushi, Maruyama Shoichi, Agatsuma Toshinori, Wada Teiji, Nishikawa Hiroyoshi

    INTERNATIONAL IMMUNOLOGY   Vol. 33 ( 8 ) page: 435 - 446   2021.8

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  32. Newly emerged immunogenic neoantigens enable to break the resistance of immune checkpoint inhibitors.

    Sugiyama Daisuke, Muramatsu Tomoaki, Noguchi Takuro, Akatsuka Yoshiki, Nishikawa Hiroyoshi

    CANCER RESEARCH   Vol. 81 ( 13 )   2021.7

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    Language:Japanese  

    Web of Science

  33. Anti-GARP antibody DS-1055a augments antitumor immunity by depleting highly suppressive GARP(+) regulatory T cells.

    Satoh Kazuki, Kobayashi Yoichi, Fujimaki Kaori, Hata Masato, Hayashi Shinko, Ishida Saori, Sugiyama Daisuke, Sato Takahiko, Kyungtaek Lim, Miyamoto Megumi, Kozuma Shiho, Kadokura Michinori, Wakita Kenichi, Hirahara Kazuki, Amano Masato, Watanabe Ichiro, Okamoto Atsushi, Tuettenberg Andrea, Jonuleit Helmut, Tanemura Atsushi, Maruyama Shoichi, Agatsuma Toshinori, Wada Teiji, Nishikawa Hiroyoshi

    CANCER RESEARCH   Vol. 81 ( 13 )   2021.7

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  34. CD4(+) T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice

    Yasuda Yoshinori, Iwama Shintaro, Sugiyama Daisuke, Okuji Takayuki, Kobayashi Tomoko, Ito Masaaki, Okada Norio, Enomoto Atsushi, Ito Sachiko, Yan Yue, Sugiyama Mariko, Onoue Takeshi, Tsunekawa Taku, Ito Yoshihiro, Takagi Hiroshi, Hagiwara Daisuke, Goto Motomitsu, Suga Hidetaka, Banno Ryoichi, Takahashi Masahide, Nishikawa Hiroyoshi, Arima Hiroshi

    SCIENCE TRANSLATIONAL MEDICINE   Vol. 13 ( 593 )   2021.5

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  35. Flow cytometry analysis of peripheral Tregs in patients with multiple myeloma under lenalidomide maintenance

    Nozaki Kenji, Fujioka Yuki, Sugiyama Daisuke, Ishikawa Jun, Iida Masato, Shibata Masaru, Kosugi Satoru, Nishikawa Hiroyoshi, Shibayama Hirohiko

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 113 ( 5 ) page: 772 - 774   2021.5

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  36. Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors.

    Kobayashi T, Iwama S, Sugiyama D, Yasuda Y, Okuji T, Ito M, Ito S, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Nishikawa H, Arima H

    Journal for immunotherapy of cancer   Vol. 9 ( 5 )   2021.5

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    Language:English  

    DOI: 10.1136/jitc-2021-002493

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  37. A simple method to distinguish residual elotuzumab from monoclonal paraprotein in immunofixation assays for multiple myeloma patients

    Chen Shurui, Kiguchi Toru, Nagata Yasuyuki, Tamai Yotaro, Ikeda Takeshi, Kajiya Ryoko, Ono Takaaki, Sugiyama Daisuke, Nishikawa Hiroyoshi, Akatsuka Yoshiki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 113 ( 4 ) page: 473 - 479   2021.4

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  38. HSP90 inhibition overcomes EGFR amplification-induced resistance to third-generation EGFR-TKIs.

    Watanabe S, Goto Y, Yasuda H, Kohno T, Motoi N, Ohe Y, Nishikawa H, Kobayashi SS, Kuwano K, Togashi Y

    Thoracic cancer   Vol. 12 ( 5 ) page: 631 - 642   2021.3

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    DOI: 10.1111/1759-7714.13839

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  39. Cancer immunotherapy -past, present, and future-

    Nishikawa Hiroyoshi, Kawakami Yutaka

    CANCER SCIENCE   Vol. 112   page: 964 - 964   2021.2

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  40. Intratumor heterogeneity characterizes immune resistance to adoptive T cell therapy

    Hinohara Kunihiko, Nishikawa Hiroyoshi

    CANCER SCIENCE   Vol. 112   page: 178 - 178   2021.2

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  41. Development of novel combination cancer immunotherapy using anti-PD-1 and anti-PD-L1 antibody

    Hasegawa Hirotaka, Sugiyama Daisuke, Kanda Mitsuro, Hayashi Masamichi, Tanaka Chie, Yamada Suguru, Nakayama Goro, Koike Masahiko, Nomoto Shuji, Fujiwara Michitaka, Kodera Yasuhiro, Nishikawa Hiroyoshi

    CANCER SCIENCE   Vol. 112   page: 741 - 741   2021.2

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  42. Potentiality of multiple modalities for single-cell analyses to evaluate the tumor microenvironment in clinical specimens.

    Kashima Y, Togashi Y, Fukuoka S, Kamada T, Irie T, Suzuki A, Nakamura Y, Shitara K, Minamide T, Yoshida T, Taoka N, Kawase T, Wada T, Inaki K, Chihara M, Ebisuno Y, Tsukamoto S, Fujii R, Ohashi A, Suzuki Y, Tsuchihara K, Nishikawa H, Doi T

    Scientific reports   Vol. 11 ( 1 ) page: 341   2021.1

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    Language:English  

    DOI: 10.1038/s41598-020-79385-w

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  43. Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies

    Nishikawa Hiroyoshi, Koyama Shohei

    JOURNAL FOR IMMUNOTHERAPY OF CANCER   Vol. 9 ( 7 )   2021

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  44. Corrigendum: Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+ T Lymphocyte Signature.

    Kelkka T, Savola P, Bhattacharya D, Huuhtanen J, Lönnberg T, Kankainen M, Paalanen K, Tyster M, Lepistö M, Ellonen P, Smolander J, Eldfors S, Yadav B, Khan S, Koivuniemi R, Sjöwall C, Elo LL, Lähdesmäki H, Maeda Y, Nishikawa H, Leirisalo-Repo M, Sokka-Isler T, Mustjoki S

    Frontiers in immunology   Vol. 12   page: 710831   2021

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    DOI: 10.3389/fimmu.2021.710831

    PubMed

  45. Cancer immunotherapy with PI3K and PD-1 dual-blockade via optimal modulation of T cell activation signal Reviewed

    Isoyama Sho, Mori Shigeyuki, Sugiyama Daisuke, Kojima Yasuhiro, Tada Yasuko, Shitara Kohei, Hinohara Kunihiko, Dan Shingo, Nishikawa Hiroyoshi

    JOURNAL FOR IMMUNOTHERAPY OF CANCER   Vol. 9 ( 8 )   2021

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  46. Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial).

    Kawazoe A, Kuboki Y, Shinozaki E, Hara H, Nishina T, Komatsu Y, Yuki S, Wakabayashi M, Nomura S, Sato A, Kuwata T, Kawazu M, Mano H, Togashi Y, Nishikawa H, Yoshino T

    Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 26 ( 22 ) page: 5887 - 5894   2020.11

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    DOI: 10.1158/1078-0432.CCR-20-1803

    PubMed

  47. Endoscopic Activity and Serum TNF-alpha Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn's Disease Patients

    Murate Kentaro, Maeda Keiko, Nakamura Masanao, Sugiyama Daisuke, Wada Hirotaka, Yamamura Takeshi, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Miyahara Ryoji, Ishigami Masatoshi, Nishikawa Hiroyoshi, Fujishiro Mitsuhiro

    INFLAMMATORY BOWEL DISEASES   Vol. 26 ( 11 ) page: 1669 - 1681   2020.11

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  48. CYBERTRACK2.0: zero-inflated model-based cell clustering and population tracking method for longitudinal mass cytometry data.

    Minoura K, Abe K, Maeda Y, Nishikawa H, Shimamura T

    Bioinformatics (Oxford, England)     2020.10

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    DOI: 10.1093/bioinformatics/btaa873

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  49. Model-based clustering for flow and mass cytometry data with clinical information

    Abe Ko, Minoura Kodai, Maeda Yuka, Nishikawa Hiroyoshi, Shimamura Teppei

    BMC BIOINFORMATICS   Vol. 21 ( Suppl 13 ) page: 393   2020.9

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  50. Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer.

    Sasaki A, Nakamura Y, Togashi Y, Kuno H, Hojo H, Kageyama S, Nakamura N, Takashima K, Kadota T, Yoda Y, Mishima S, Sawada K, Kotani D, Kawazoe A, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Yano T, Kobayashi T, Akimoto T, Nishikawa H, Shitara K

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   Vol. 23 ( 5 ) page: 893 - 903   2020.9

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    DOI: 10.1007/s10120-020-01058-4

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  51. The status of the tumor microenvironment changes dynamics of the balance of CD8(+) T cells and Treg cells in renal cell carcinoma

    Sugiyama Daisuke, Muramatsu Tomoaki, Kobayashi Yoichi, Sassa Naoto, Maruyama Shoichi, Goto Momokazu, Akatsuka Yoshiki, Nishikawa Hiroyoshi

    CANCER RESEARCH   Vol. 80 ( 16 )   2020.8

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  52. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603).

    Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology   Vol. 38 ( 18 ) page: 2053 - 2061   2020.6

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    Language:English  

    DOI: 10.1200/JCO.19.03296

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  53. TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma.

    Bando H, Kotani D, Tsushima T, Hara H, Kadowaki S, Kato K, Chin K, Yamaguchi K, Kageyama SI, Hojo H, Nakamura M, Tachibana H, Wakabayashi M, Fukutani M, Togashi Y, Fuse N, Nishikawa H, Kojima T

    BMC cancer   Vol. 20 ( 1 ) page: 336   2020.4

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    DOI: 10.1186/s12885-020-06716-5

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  54. Influence of Percutaneous Occlusion of Atrial Septal Defect on Left Atrial Function Evaluated Using 2D Speckle Tracking Echocardiography

    Suzuki Kazutaka, Kato Taichi, Koyama Satoshi, Shinohara Tsutomu, Inukai Sachiko, Sato Jun, Yamamoto Hidenori, Omori Daisuke, Yoshida Shuichiro, Takeda Sho, Nishikawa Hiroshi, Ohashi Naoki, Sakurai Hajime, Saitoh Shinji

    INTERNATIONAL HEART JOURNAL   Vol. 61 ( 1 ) page: 83 - 88   2020.1

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    Language:Japanese  

    DOI: 10.1536/ihj.19-173

    Web of Science

  55. Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+ T Lymphocyte Signature.

    Kelkka T, Savola P, Bhattacharya D, Huuhtanen J, Lönnberg T, Kankainen M, Paalanen K, Tyster M, Lepistö M, Ellonen P, Smolander J, Eldfors S, Yadav B, Khan S, Koivuniemi R, Sjöwall C, Elo LL, Lähdesmäki H, Maeda Y, Nishikawa H, Leirisalo-Repo M, Sokka-Isler T, Mustjoki S

    Frontiers in immunology   Vol. 11   page: 578848   2020

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    DOI: 10.3389/fimmu.2020.578848

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  56. Model-based cell clustering and population tracking for time-series flow cytometry data

    Minoura Kodai, Abe Ko, Maeda Yuka, Nishikawa Hiroyoshi, Shimamura Teppei

    BMC BIOINFORMATICS   Vol. 20 ( 1 ) page: 633   2019.12

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  57. A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors

    Doi Toshihiko, Muro Kei, Ishii Hiroshi, Kato Terufumi, Tsushima Takahiro, Takenoyama Mitsuhiro, Oizumi Satoshi, Gemmoto Kazuto, Suna Hideaki, Enokitani Kouki, Kawakami Tetsuyoshi, Nishikawa Hiroyoshi, Yamamoto Noboru

    CLINICAL CANCER RESEARCH   Vol. 25 ( 22 ) page: 6614 - 6622   2019.11

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  58. Primary tumor resection after nivolumab treatment for metastatic renal cell carcinoma: A case report

    Tanegashima Tokiyoshi, Tsukahara Shigehiro, Ikenoue Takashi, Otsubo Satoshi, Hasehawa Shuji, Nishikawa Hiroyoshi, Eto Masatoshi

    ANNALS OF ONCOLOGY   Vol. 30   2019.10

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    Language:Japanese  

    DOI: 10.1093/annonc/mdz343.077

    Web of Science

  59. Tumor-infiltrating lymphocytes in renal cancer patients demonstrate a diverse PD-1 expression and characteristic Treg classification

    Sugiyama Daisuke, Muramatsu Tomoaki, Kobayashi Yoichi, Sassa Naoto, Maruyama Shoichi, Goto Momokazu, Akatsuka Yoshiki, Nishikawa Hiroyoshi

    CANCER RESEARCH   Vol. 79 ( 13 )   2019.7

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  60. Analysis of the Tumor Reactivity of Tumor-Infiltrating Lymphocytes in a Metastatic Melanoma Lesion that Lost Major Histocompatibility Complex Class I Expression after Anti-PD-1 Therapy

    Inozume Takashi, Yaguchi Tomonori, Ariyasu Ryo, Togashi Yosuke, Ohnuma Takehiro, Honobe Akiko, Nishikawa Hiroyoshi, Kawakami Yutaka, Kawamura Tatsuyoshi

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   Vol. 139 ( 7 ) page: 1490 - 1496   2019.7

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  61. Reprogramming the Tumor Microenvironment to Improve Immunotherapy: Emerging Strategies and Combination Therapies.

    Datta M, Coussens LM, Nishikawa H, Hodi FS, Jain RK

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting   Vol. 39   page: 165 - 174   2019.1

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    DOI: 10.1200/EDBK_237987

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  62. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan.

    Takahashi N, Nishiwaki K, Nakaseko C, Aotsuka N, Sano K, Ohwada C, Kuroki J, Kimura H, Tokuhira M, Mitani K, Fujikawa K, Iwase O, Ohishi K, Kimura F, Fukuda T, Tanosaki S, Takahashi S, Kameoka Y, Nishikawa H, Wakita H, STAT study group.

    Haematologica   Vol. 103 ( 11 ) page: 1835 - 1842   2018.11

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    Language:English  

    DOI: 10.3324/haematol.2018.194894

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  63. Possible Biomarker for immune checkpoint inhibitor

    Takeuchi Yoshiko, Nishikawa Hiroyoshi

    ANNALS OF ONCOLOGY   Vol. 28   page: 20 - 20   2017.10

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    Web of Science

  64. Regulatory T cells, as a target in anticancer immunotherapy

    Enokida Tomohiro, Nishikawa Hiroyoshi

    IMMUNOTHERAPY   Vol. 9 ( 8 ) page: 623 - 627   2017.6

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  65. NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC

    Takeoka Tomohira, Nagase Hirotsugu, Kurose Koji, Ohue Yoshihiro, Yamasaki Makoto, Takiguchi Shuji, Sato Eiichi, Isobe Midori, Kanazawa Takayuki, Matsumoto Mitsunobu, Iwahori Kota, Kawashima Atsunari, Morimoto-Okazawa Akiko, Nishikawa Hiroyoshi, Oka Mikio, Pan Linda, Venhaus Ralph, Nakayama Eiichi, Mori Masaki, Doki Yuichiro, Wada Hisashi

    JOURNAL OF IMMUNOTHERAPY   Vol. 40 ( 4 ) page: 140 - 147   2017.5

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  66. Regulatory T cells: A target in anticancer immunotherapy.

    Enokida T, Nishikawa H

    Nihon rinsho. Japanese journal of clinical medicine   Vol. 75 ( 2 ) page: 181 - 187   2017.2

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    PubMed

  67. Regulatory T Cells: Molecular and Cellular Basis for Immunoregulation

    Togashi Yosuke, Nishikawa Hiroyoshi

    EMERGING CONCEPTS TARGETING IMMUNE CHECKPOINTS IN CANCER AND AUTOIMMUNITY   Vol. 410   page: 3 - 27   2017

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  68. Roles of regulatory T cells in cancer immunity

    Takeuchi Yoshiko, Nishikawa Hiroyoshi

    INTERNATIONAL IMMUNOLOGY   Vol. 28 ( 8 ) page: 401 - 409   2016.8

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Books 7

  1. 標準免疫学 第4版

    宮坂昌之,小安重夫,椛島健治,改正恒康,西川博嘉他( Role: Contributor)

    株式会社医学書院  2021.3  ( ISBN:978-4-260-04238-3

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    Total pages:416   Language:Japanese Book type:Textbook, survey, introduction

  2. 免疫・炎症病態X治療Update

    熊ノ郷淳,西川博嘉他( Role: Contributor)

    南山堂  2019.5  ( ISBN:4525167815

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    Total pages:252   Language:Japanese Book type:Scholarly book

  3. 新臨床腫瘍学 改訂第5版

    石岡千加史、土屋直人、新井康仁、大場雄介、曽和義広、田原栄俊、鈴木拓、小坂展慶、二口充、樋口京子、平尾敦、野口耕司、西川博嘉 他( Role: Contributor)

    南江堂  2018.7  ( ISBN:978-4-524-23788-3

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    Total pages:872   Language:Japanese Book type:Scholarly book

  4. 実験医学 Vol.36 No.9 2018(通巻617号) 特集:がんは免疫系をいかに抑制するのか

    西川博嘉、河上裕、町山裕亮、石田靖雅、前田優香、吉永正憲、竹内理、高塚奈津子、茶本健司、冨樫庸介( Role: Joint author)

    羊土社  2018.6  ( ISBN:4758125082

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    Total pages:139   Language:Japanese Book type:Scholarly book

  5. 免疫学コア講義 改訂4版

    熊ノ郷淳,阪口薫雄,竹田 潔,吉田裕樹,田中稔之,改正恒康,西川博嘉,他( Role: Contributor ,  がん免疫と移植免疫)

    南山堂  2017.11  ( ISBN:9784525167547

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    Total pages:309   Language:Japanese Book type:Textbook, survey, introduction

  6. がん免疫療法-What's now and what's next?-(遺伝子医学MOOK31号)

    珠玖 洋 , 池田 裕明 , 影山 愼一 , 西川 博嘉 他( Role: Joint editor)

    メディカルドゥ  2017.7  ( ISBN:9784944157617

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    Total pages:292   Language:Japanese Book type:Scholarly book

  7. がん免疫療法ハンドブック 第1版

    上田龍三、西川博嘉( Role: Joint author)

    メディカルレビュー  2016.7  ( ISBN:9784779217166

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    Total pages:223   Language:Japanese Book type:Scholarly book

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Research Project for Joint Research, Competitive Funding, etc. 5

  1. がん免疫療法抵抗性を解除する新規治療法の臨床展開に向けた開発研究

    2019.4 - 2022.3

    国立研究開発法人国立がん研究センター がん研究開発費 

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    Grant type:Competitive

  2. 腸内細菌叢のがん免疫応答への関わりの解明によるがん治療への展開

    2016.9 - 2022.3

    日本医療研究開発機構研究費 (革新的先端研究開発支援事業 AMED-CREST) 

    西川博嘉

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    Grant type:Competitive

    抗腫瘍免疫応答への腸内細菌叢の影響を検討する

  3. がん細胞および免疫応答解析に基づくがん免疫療法効果予測診断法の確立

    2016.9 - 2022.3

    日本医療研究開発機構研究費 (次世代がん医療創生研究事業) 

    西川博嘉

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    Grant type:Competitive

    がん免疫療法のバイオマーカーを同定する研究

  4. 先端的がん免疫モニタリング法開発体制に関する研究

    2016.4 - 2019.3

    国立研究開発法人国立がん研究センター がん研究開発費 

    西川博嘉

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    Grant type:Competitive

    新たな免疫モニタリング方法を開発する研究

  5. T細胞応答の多様性回復による がん免疫併用療法の開発

    2015.9 - 2018.3

    日本医療研究 開発機構研究費 (革新的がん医療実用化研究事業) 

    西川博嘉

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    Grant type:Competitive

    T細胞の多様性回復を期待した新規創薬研究

KAKENHI (Grants-in-Aid for Scientific Research) 8

  1. 発がんの人種差と免疫応答の関わりの解明

    2017.5 - 2022.3

    科学研究費補助金  基盤研究(S)

    西川 博嘉

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    Authorship:Principal investigator 

  2. がん抗原特性に基づく免疫抑制機構解明による新規がん免疫療法開発の基盤研究

    2017.4 - 2018.3

    科学研究費補助金  基盤研究(A)

    西川 博嘉

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    がん免疫療法の成功は、がん細胞に対して成立した免疫寛容を免疫監視の状態に戻す免疫操作により、がん治療が可能であることを示した。しかし、依然として現行のがん免疫療法の臨床効果は20-30%程度の患者でしか認められず、限定的である。よってより効果的ながん免疫療法を開発するとともに、レスポンダーを層別化するバイオマーカーを同定することが緊喫の課題であると考えられ、抗腫瘍免疫応答の本態を解明することが極めて重要である。がん局所に存在するがん抗原特異的CD8+T細胞の認識抗原の差異に着目し、免疫抑制機構の違いを解明すべく検討を開始した。遺伝子変異の蓄積により生じたがん細胞内には、正常細胞が本来もっていない非自己の物質ががん抗原として存在する。まずは、がん抗原特異的T細胞応答の検討が必須であることから、がん細胞が持つ遺伝子変異に由来するがん抗原(ネオがん抗原)に対するT細胞誘導の系を少量の血液検体で実施するための系を確立した。これらのネオがん抗原を認識するT細胞の中でもT 細胞レセプター(TCR)の親和性により活性化状態が異なり、免疫抑制機構への感受性が異なることの予備的データを得ることができた。興味深いことにこれらのがん細胞の遺伝子変異に由来するがん抗原は、ドライバー遺伝子由来のものは存在せず、検討した全てがパッセンジャー遺伝子変異に由来していた。つまりドライバー遺伝子変異が免疫系の標的となると、がん細胞は抗原脱落等により逃れることができないため免疫系のプレッシャーがきつく発がんできない可能性が示唆され、今後の基盤研究Sでの発がんの人種差(HLA差)と免疫応答との関連を明らかにする研究につなげていく。

  3. 悪性黒色腫の新規免疫的解析に基づくがん免疫療法継続基準の開発

    2016.4 - 2018.3

    科学研究費補助金  挑戦的萌芽研究

    西川 博嘉

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    本研究では、免疫チェックポイント阻害剤治療に対するレスポンダーおよびノンレスポンダー患者検体を用いた免疫応答の比較検討により、臨床効果と関わる免疫応答を検討した。末梢血を用いた網羅的な免疫関連分子発現解析により、CD4陽性CD27陽性Fas陰性セントラルメモリーT細胞の治療後の増加が治療効果と相関することが明らかになった。また腫瘍局所の解析では、レスポンダーではエフェクターのCD8陽性T細胞、ノンレスポンダーではCD4陽性制御性T細胞が優位となっていることが示され、今後は多数症例や前向きでの検討を実施し、薬剤投与の判断基準に展開する。

  4. 制御性T細胞の選択的コントロールによる抗腫瘍免疫応答の賦活化

    2014.4 - 2017.3

    科学研究費補助金  基盤研究(B)

    西川 博嘉

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    自己に対する免疫応答を制御している制御性T細胞(Tregs)が、がん抗原に対する免疫応答を抑制している。Tregsがとりわけ自己由来のがん抗原特異的CD8+T細胞誘導に与える影響を解析した。Tregsは抗原提示細胞の共刺激シグナルを制御することで、がん抗原特異的CD8+T細胞を特徴的なフェノタイプを有する免疫不応答(アネルギー)状態に陥れることを示した。これらのがん抗原特異的CD8+T細胞の不応答状態は安定的であることから、効果的ながん免疫療法にはTregsの免疫抑制を克服した上でのがん抗原に対する免疫応答の活性化が極めて重要であると考えられた

  5. 大腸癌の新規免疫的分類に基づくがん免疫治療の選択的適応基準の開発

    2014.4 - 2016.3

    科学研究費補助金  挑戦的萌芽研究

    西川 博嘉

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    Authorship:Principal investigator 

    従来、制御性T細胞と見なされていたFOXP3陽性細胞の中に、FOXP3を弱発現する細胞群が多数存在することを明らかにした。FOXP3を弱発現する細胞群は、抑制能を持たない活性型T細胞であり、大腸癌に付着する腸内細菌により腫瘍内で増加した炎症性サイトカインによって誘導されることを解明した。さらに、この様なFOXP3を弱発現する細胞群が多数浸潤する大腸癌は予後が良好である一方、抑制活性をもつ制御性T細胞が多数浸潤する大腸癌は他のがん腫と同様に、制御性T細胞の浸潤が予後不良因子になることを示した。

  6. 腫瘍局所での制御性T細胞による免疫抑制機構の解析

    2011.4 - 2014.3

    科学研究費補助金  基盤研究(B)

    西川 博嘉

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    Authorship:Principal investigator 

    がん組織に多数存在する制御性T細胞(Treg)の特徴を分子レベルで検討したところ、腫瘍浸潤Tregは活性型であり、ケモカインレセプターの1種(CCR4)が高発現していた。CCR4を標的としてTreg除去を試みたところ、腫瘍局所に浸潤する活性化Tregが選択的に除去され、がん抗原特異的CD4およびCD8+T細胞応答が誘導・増強した。また、Tregによって抑制されたCD8+T細胞を解析したところ、これらのT細胞が特徴的な分子マーカーを発現することから、Treg抑制の新たな機構の可能性が示唆された。

  7. 細菌ベクターを用いた新規がんワクチン療法の開発

    2008 - 2009

    科学研究費補助金  特定領域研究

    西川 博嘉

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    Authorship:Principal investigator 

    昨年度S.typhimuriumによCD4+CD25+制御性T細胞(Treg)の免疫抑制解除には、GITRシグナルが重要な働きを果たしていることを明らかにした。この成果をもとに臨床応用を促進するため、GITRシグナルを提供できる抗体を用いた免疫療法の検討を行った。ヒトがん抗原であるNY-ESO-1モデルマウスを用いて、抗GITR抗体(アゴニスティック)の抗腫瘍活性を検討した。抗GITR抗体単独では、抗腫瘍効果は限られたものだった。そこで他の免疫共刺激分子との併用を試みた。なかでも抗CTLA-4抗体による抑制シグナルブロックとの併用は、強い抗腫瘍活性を示し、既に10mm大に到達した腫瘍を拒絶可能であった。
    NY-ESO-1モデルマウスを用いていことから、NY-ESO-1特異的CD8+細胞傷害性T細胞(CTL)をシングルセルレベルで検出可能である。ことを用いて強い抗腫瘍活性のメカニズムを検討した。現在まで免疫共刺激分子は、細胞増殖、サイトカイン産生を刺激することが明らかとなっていたが、このマウスモデルを用いることにより、GITR分子シグナル刺激とCTLA-4分子シグナルブロックは異なる2つの活性化シグナルをT細胞に提供していることが明らかになった。すなわち、CTLA-4分子のブロックにより細胞増殖が主に刺激され、GITR分子刺激によりサイトカイン産生およびTreg抵抗性が獲得された。つまり、両者を併用することにより、Treg抵抗性を獲得したNY-ESO-1特異的CD8+CTLの増殖が効率的に刺激され、腫瘍局所に多数浸潤していることが明らかとなった。

  8. サルモネラベクターを用いた制御性T細胞抑制機構の解明と新規癌ワクチン療法の開発

    2007 - 2008

    科学研究費補助金 

    西川 博嘉

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    Authorship:Principal investigator 

    本研究において,S.typhimurium-NY-ESO-1を用いて,ヒト及びマウスモデルにおいて,Tregの抑制作用を解除し,ヒト癌抗原,NY-ESO-1に対する特異的免疫応答が效果的に誘導しえるかを検討した。ヒトにおいて,我々が開発したCD4^+CD25^+Treg活性の新規アッセイ方法により,CD4^+CD25^+Treg存在下に
    S.typhimurium-NY-ESO-1を用いて末梢血CD4^+T細胞よりNY-ESO-1特異的CD4^+ヘルパーT細胞(Th)の誘導の可否を測定することで,S.tvphimurium-NY-ESO-1のTreg抑制解除效果を検討したところ,S.typhimurium-NY-ESO-1はTreg存在下にNY-ESO-1特異的Thを誘導した。またTregの抑制解除の詳細なメカニズムを,種々のサイトカイン,Tregの抑制効果に関わる分子シグチルのブロッキングにより検討した。これにより,IL-6及びGITRシグナルがS. typhimuriumによるTreg抑制機能解除に極めて重要な役割を果たしていることを明らかにした。さらに,Treg抑制機能解除効果が明らかとなったGITRシグナルを用いたがんワクチン療法をマウスモデルにより確認した。すなわち,GITR ligand (GITRL)をCytotoxic T lymphocytes (CTL)抗原とともに免疫することにより,特異的CD8^+T細胞誘導,腫瘍拒絶効果の増強が認められた。また腫瘍拒絶効果の増強は,GITRシグナルによりTreg抵抗性の特異的CD8^+T細胞が誘導されたことによることを明らかにした。

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Teaching Experience (On-campus) 6

  1. Natural Environment and the Human Being

    2020

  2. 免疫と生体防御

    2020

  3. 免疫と生体防御

    2019

  4. 免疫と生体防御

    2018

  5. 免疫と生体防御

    2017

  6. 免疫と生体防御

    2016

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