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Developing novel immunotherapy against nasal NK/T cell lymphoma

Research Project

Project/Area Number 18H02948
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionAsahikawa Medical College

Principal Investigator

Harabuchi Yasuaki  旭川医科大学, 医学部, 教授 (80208686)

Co-Investigator(Kenkyū-buntansha) 熊井 琢美  旭川医科大学, 医学部, 特任講師 (00596306)
高原 幹  旭川医科大学, 医学部, 講師 (50322904)
大栗 敬幸  旭川医科大学, 医学部, 准教授 (70564061)
長門 利純  旭川医科大学, 医学部, 講師 (80431419)
岸部 幹  旭川医科大学, 医学部, 講師 (80447101)
小林 博也  旭川医科大学, 医学部, 教授 (90280867)
大原 賢三  旭川医科大学, 医学部, 助教 (20596308)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsNK/T細胞リンパ腫 / 免疫チェックポイント / ペプチドワクチン / 鼻性NK/T細胞リンパ腫 / EBウイルス / 腫瘍抗原 / 免疫抑制 / 免疫療法
Outline of Final Research Achievements

Nasal NK/T cell lymphoma is an EB virus-related malignancy mainly observed in the Asian countries. We have previously discovered that this lymphoma has a cross-talk between immune cells. In this study, we provide the evidence that immune regulatory mechanism plays a role in supporting lymphoma cells, and established a novel immunotherapeutic approach. Specifically, negative immune checkpoint including PD-1/PD-L1 interaction plays an essential role in lymphoma-mediated immunosuppression. In addition, we found novel epitope peptides from lymphoma-associated antigens. These results indicating that peptide vaccine using novel epitope peptides combined with immune checkpoint blockade could be an interesting strategy to treat nasal NK/T cell lymphoma.

Academic Significance and Societal Importance of the Research Achievements

鼻性NK/T細胞リンパ腫は、日本を含むアジア圏に多い難治性の疾患である。進行例においては多剤併用化学療法を用いて予後不良であり、新規治療法の開発が望まれている。今回われわれは、現在各分野で注目を集めている免疫チェックポイント分子の本リンパ腫における発現や意義について解析した。また、新たな免疫治療の一つであるペプチドワクチンに着目し、新たな腫瘍抗原由来のエピトープペプチドを複数同定した。これらの結果は、本リンパ腫に患者に免疫チェックポイント阻害薬およびペプチドワクチンの併用両方の根拠となり得る画期的な発見である。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (45 results)

All 2021 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (33 results) (of which Int'l Joint Research: 11 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery2021

    • Author(s)
      Kono Michihisa、Kumai Takumi、Hayashi Ryusuke、Yamaki Hidekiyo、Komatsuda Hiroki、Wakisaka Risa、Nagato Toshihiro、Ohkuri Takayuki、Kosaka Akemi、Ohara Kenzo、Kishibe Kan、Takahara Miki、Katada Akihiro、Hayashi Tatsuya、Celis Esteban、Kobayashi Hiroya、Harabuchi Yasuaki
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: epub Issue: 12 Pages: 3421-3434

    • DOI

      10.1007/s00262-021-02940-5

    • Related Report
      2020 Annual Research Report
  • [Journal Article] A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment2021

    • Author(s)
      Nagata Marino、Kosaka Akemi、Yajima Yuki、Yasuda Syunsuke、Ohara Mizuho、Ohara Kenzo、Harabuchi Shohei、Hayashi Ryusuke、Funakoshi Hiroshi、Ueda Jun、Kumai Takumi、Nagato Toshihiro、Oikawa Kensuke、Harabuchi Yasuaki、Esteban Celis、Ohkuri Takayuki、Kobayashi Hiroya
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: epub Issue: 8 Pages: 2301-2312

    • DOI

      10.1007/s00262-021-02864-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma2020

    • Author(s)
      Hayashi Ryusuke、Nagato Toshihiro、Kumai Takumi、Ohara Kenzo、Ohara Mizuho、Ohkuri Takayuki、Hirata-Nozaki Yui、Kosaka Akemi、Yasuda Syunsuke、Oikawa Kensuke、Kono Michihisa、Kishibe Kan、Takahara Miki、Katada Akihiro、Hayashi Tatsuya、Celis Esteban、Harabuchi Yasuaki、Kobayashi Hiroya et al
    • Journal Title

      OncoImmunology

      Volume: 10 Issue: 1 Pages: 1856545-1856545

    • DOI

      10.1080/2162402x.2020.1856545

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer.2019

    • Author(s)
      Ohara M, Ohara K, Kumai T, Ohkuri T, Nagato T, Hirata-Nozaki Y, Kosaka A, Nagata M, Hayashi R, Harabuchi S, Yajima Y, Oikawa K, Harabuchi Y, Sumi Y, Furukawa H, Kobayashi H.
    • Journal Title

      Cancer Immunol Immunother.

      Volume: ePub Issue: 6 Pages: 989-999

    • DOI

      10.1007/s00262-020-02524-9

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intratumoral STING activations overcome negative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma.2019

    • Author(s)
      Harabuchi S, Kosaka A, Yajima Y, Nagata M, Hayashi R, Kumai T, Ohara K, Nagato T, Oikawa K, Ohara M, Harabuchi Y, Ohkuri T, Kobayashi H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 522 Issue: 2 Pages: 408-414

    • DOI

      10.1016/j.bbrc.2019.11.107

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 鼻性NK/T細胞リンパ腫2019

    • Author(s)
      高原 幹
    • Journal Title

      Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology)

      Volume: 58 Issue: 1 Pages: 85-87

    • DOI

      10.7248/jjrhi.58.85

    • NAID

      130007636288

    • ISSN
      0910-9153, 1883-7077
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 頭頸部癌に対する癌ペプチドワクチン療法の開発2019

    • Author(s)
      熊井 琢美
    • Journal Title

      Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology)

      Volume: 58 Issue: 1 Pages: 107-108

    • DOI

      10.7248/jjrhi.58.107

    • NAID

      130007636230

    • ISSN
      0910-9153, 1883-7077
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma.2019

    • Author(s)
      Hirata-Nozaki Y, Ohkuri T, Ohara K, Kumai T, Nagata M, Harabuchi S, Kosaka A, Nagato T, Ishibashi K, Oikawa K, Aoki N, Ohara M, Harabuchi Y, Uno Y, Takei H, Celis E, Kobayashi H.
    • Journal Title

      J Transl Med.

      Volume: 17 Issue: 1

    • DOI

      10.1186/s12967-019-1957-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: Basic Science and Clinical Progress2019

    • Author(s)
      Harabuchi Yasuaki、Takahara Miki、Kishibe Kan、Nagato Toshihiro、Kumai Takumi
    • Journal Title

      Frontiers in Pediatrics

      Volume: 7 Pages: 141-141

    • DOI

      10.3389/fped.2019.00141

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin-dependent kinase 1 and survivin as potential therapeutic targets against nasal natural killer/T-cell lymphoma2019

    • Author(s)
      Nagato Toshihiro、Ueda Seigo、Takahara Miki、Kishibe Kan、Komabayashi Yuki、Kumai Takumi、Ohara Kenzo、Hirata-Nozaki Yui、Harabuchi Shohei、Hayashi Ryusuke、Ohkuri Takayuki、Bernasconi Michele、Nadal David、Kobayashi Hiroya、Harabuchi Yasuaki
    • Journal Title

      Laboratory Investigation

      Volume: 99 Issue: 5 Pages: 612-624

    • DOI

      10.1038/s41374-018-0182-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 鼻性NK/T細胞リンパ腫に対する革新的免疫療法の開発2018

    • Author(s)
      長門 利純、熊井 琢美,、高原 幹、大栗 敬幸、小林 博也、Celis Esteban、原渕 保明
    • Journal Title

      耳鼻咽喉科免疫アレルギー

      Volume: 36 Pages: 15-22

    • NAID

      130006619256

    • Related Report
      2018 Annual Research Report
  • [Presentation] 頭頸部癌に対する癌ペプチドワクチン療法の開発2019

    • Author(s)
      熊井琢美
    • Organizer
      第32回日本耳鼻咽喉科学会北海道地方部会ブロック講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] PD-L1を標的とした頭頸部扁平上皮癌に対する癌免疫療法に関する研究2019

    • Author(s)
      野﨑 結
    • Organizer
      第35回旭川集談会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sustained persistence of IL-2 signaling enhances the antitumor effect of peptide vaccines2019

    • Author(s)
      Kumai T, Sultan H, Harabuchi Y, Celis E
    • Organizer
      American Assiciation for Cancer Research Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression and function of Epstein-Barr virus-encoded microRNAs in nasal natural killer/ T-cell lymphoma2019

    • Author(s)
      Kishibe K, Komabayashi Y, Hayashi R, Kumai T, Takahara M, Harabuchi Y
    • Organizer
      ISIAN・IRS・ARS (RhinoWorld Chicago 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of cyclin-dependent kinase 1 and survivin in nasal natural killer/T-cell lymphoma2019

    • Author(s)
      Hayashi R, Nagato T, Harabuchi S, Kumai T, Kishibe K, Takahara M, Kobayashi H, Harabuchi Y
    • Organizer
      ISIAN・IRS・ARS (RhinoWorld Chicago 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Arterial infusion chemotherapy from superficial temporal artery in combination with radiotherapy for early stage nasal NK/T cell lymphoma2019

    • Author(s)
      Wakisaka R, Takahara M, Kishibe K, Katada A, Hayashi T, Harabuchi Y
    • Organizer
      ISIAN・IRS・ARS (RhinoWorld Chicago 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 鼻性NK/T細胞リンパ腫におけるCD27の発現2019

    • Author(s)
      長門利純, 林 隆介, 原渕翔平, 野﨑 結, 大原賢三, 熊井琢美, 岸部 幹, 高原 幹, 小林博也, 原渕保明
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] リン酸化抗原特異的T細胞を利用した悪性腫瘍に対するペプチドワクチン療法の基礎的解析2019

    • Author(s)
      大原賢三, 熊井琢美, 長門利純, 林 隆介, 原渕翔平, 小林博也, 原渕保明
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫における免疫抑制サイトカインの検討2019

    • Author(s)
      熊井琢美, 長門利純, 岸部 幹, 高原 幹, 青木直子, 及川賢輔, 林 達哉, 小林博也, 原渕保明
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫67症例の臨床学的検討2019

    • Author(s)
      高原 幹, 熊井琢美, 岸部 幹, 片田彰博, 林 達哉, 原渕保明
    • Organizer
      第33回ヘルペスウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫におけるCDK1とサバイビンの発現2019

    • Author(s)
      熊井琢美, 長門利純, 高原 幹, 原渕保明
    • Organizer
      第33回ヘルペスウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫67症例の臨床学的検討2019

    • Author(s)
      高原 幹, 熊井琢美, 岸部 幹, 片田彰博, 林 達哉, 原渕保明
    • Organizer
      第16回EBウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫および上咽頭癌におけるCD74とMIFの発現2019

    • Author(s)
      熊井琢美, 林 隆介, 長門利純, 原渕翔平, 岸部 幹, 高原 幹, 永田真莉乃, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也, 原渕保明
    • Organizer
      第16回EBウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫におけるCD74とMIFの発現2019

    • Author(s)
      林 隆介, 長門利純, 原渕翔平, 熊井琢美, 岸部 幹, 高原 幹, 小林博也, 原渕保明
    • Organizer
      第58回日本鼻科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Expression of cell surface CD74 and macrophage migration inhibitory factor in malignant tumors of head and neck region2019

    • Author(s)
      Hayashi R, Nagato T, Kumai T, Nagata M, Harabuchi S, Yajima Y, Kosaka A, Ohkuri T, Oikawa K, Kishibe K, Takahara M, Harabuchi Y, Kobayashi H
    • Organizer
      第78回日本癌学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌特異的な翻訳後修飾を受けたp53タンパク質は特異的T細胞応答を惹起する2019

    • Author(s)
      大原賢三, 大栗敬幸, 長門利純, 小林博也
    • Organizer
      第23回日本がん免疫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cancer Immunity Cycleと化学療法2019

    • Author(s)
      原渕翔平, 大原賢三, 野﨑 結, 熊井琢美, 長門利純, 林 達哉, 小林博也, 原渕保明
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 頭頸部悪性腫瘍におけるCD74の発現2019

    • Author(s)
      林 隆介, 長門利純, 永田真莉乃, 原渕翔平, 大原賢三, 大原みずほ, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス扁平上皮癌モデルを用いた、化学療法とSTING活性化療法の併用に関する基礎研究2019

    • Author(s)
      原渕翔平, 大栗敬幸, 小坂 朱, 永田真莉乃, 林 隆介, 大原賢三, 大原みずほ, 長門利純, 及川賢輔, 小林博也
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫における免疫抑制サイトカインの検討2019

    • Author(s)
      熊井 琢美、長門 利純、林 隆介、原渕 翔平、岸部 幹、高原 幹、林 達哉、小林 博也、原渕 保明
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Special Lecture1: Clinical, pathologic and Epstein-Barr virus features of nasal NK/T cell lymphoma2018

    • Author(s)
      Harabuchi Y
    • Organizer
      The 55th Korean Rhinologic Society Annual Congress (KRS)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinical inverstigation of 64 pationts with nasal NK/T-cel lymphoma2018

    • Author(s)
      Takahara M, Nagato T, Kishibe K, Katada A, Hayashi T, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression and function of Epstein-Barr virus-encoded microRNAs in nasal natural killer/T-cell lymphoma2018

    • Author(s)
      Kishibe K, Komabayashi Y, Kumai T, Nagato T, Takahara M, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of programmed death-ligand 1 in nasal natural killer/T-cell lymphoma2018

    • Author(s)
      Nagato t, Ohkuri T, Ohara K, Nozaki Y, Kishibe K, Takahara M, Kumai T, Araki D, Komabayashi H, Kobayashi H, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The identification of extranodal NK/T cell lymphoma, nasal type-associated antigen for helper T cell-based immunotherapy2018

    • Author(s)
      Kumai T, Komatsuda H, Araki D, Nagato T, Kishibe K, Takahara M, Hayashi T, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A clinical and pathological characterization of Epstein-Barr virus positive methotrexate-associated lymphoproliferative disorders for seven cases2018

    • Author(s)
      Araki D, Kumai T, Nagato T, Kishibe K, Takahara M, Katada A, Hayashi T, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Diagnostic values of circulating Epstein-Barr virus-encoded microRNAs as potential biomarkers for nasal natural killer/T-cell lymphoma2018

    • Author(s)
      Komatsuda H, Kishibe K, Komabayashi Y, Nagato T, Takahara M, Harabuchi Y
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍シンポジウム:「鼻副鼻腔悪性腫瘍の病態・診断・治療 up to date」鼻性NK/T細胞リンパ腫2018

    • Author(s)
      高原 幹
    • Organizer
      第57回日本鼻科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ワークショップ10:「病理学的解析が拓くがん免疫研究の進展と未来」鼻性NK/T細胞リンパ腫における免疫抑制機構の解明と新規免疫療法の開発2018

    • Author(s)
      長門 利純、原渕 保明、小林 博也
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫におけるCDK1とサバイビンの発現2018

    • Author(s)
      長門 利純、大原 賢三、原渕 翔平、林 隆介、大栗 敬幸、永田 真莉乃、大原 みずほ、小坂 朱、青木 直子、及川 賢輔、原渕 保明、小林 博也
    • Organizer
      第51回北海道病理談話会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EBウイルス陽性鼻性NK/T細胞リンパ腫に対するペプチドワクチン療法の開発2018

    • Author(s)
      原渕 翔平、熊井 琢美、長門 利純、林 達哉、原渕保明
    • Organizer
      第57回日本鼻科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫に対する放射線同時併用動注化学療法2018

    • Author(s)
      脇坂 理紗、高原 幹、長門 利純、岸部 幹、片田 彰博、林 達哉、原渕保明
    • Organizer
      第57回日本鼻科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫における免疫抑制サイトカインの検討2018

    • Author(s)
      熊井 琢美、長門 利純、岸部 幹、高原 幹、青木 直子、及川 賢輔、林 達哉、小林 博也、原渕 保明
    • Organizer
      第15回EBウイルス研究会
    • Related Report
      2018 Annual Research Report
  • [Book] 今日の耳鼻咽喉科・頭頸部外科治療指針 第4版(森山 寛, 大森孝一, 藤枝重治, 小島博己, 猪原秀典編)頭頸部領域の悪性リンパ腫2018

    • Author(s)
      長門利純
    • Publisher
      医学書院
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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