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Genetic alterations and expressions of immune check point molecules in salivary gland cancer

Research Project

Project/Area Number 17K11384
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionKobe University

Principal Investigator

Kiyota Naomi  神戸大学, 医学部附属病院, 特命准教授 (40515037)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords唾液腺癌 / 遺伝子変化 / 免疫チェックポイント / 頭頸部癌 / 免疫チェックポイント分子 / 免疫チェックポイント阻害薬 / 腫瘍免疫 / 癌 / 免疫学 / 遺伝子
Outline of Final Research Achievements

Total of 35 cases with salivary gland cancer were analyzed. The pathological types of these cases are mucoepidermoid carcinoma(MEC) low-grade, high-grade, salivary duct carcinoma(SDC), adenocarcinoma (ANOS) and adenoid cystic carcinoma (ACC) and 7 cases in each.
Genetic analyses were performed with Oncomine Tumor Mutation Load Assay and multiplex immunohistochemistry was performed with CD3/CD4/CD8/CD204/FOXP3/PD-L1/PD-L2. Tumor mutational load appeared to be higher in MEC-high, SDC and ANOS. From the multiplex immunohistochemistry analysis, intra-tumor Treg and PD-L1 positive cell were suggested to be poor prognostic factors for disease-free survival irrespective of pathological subtypes.

Academic Significance and Societal Importance of the Research Achievements

唾液腺癌は希少がんであり手術以外に標準的治療はなく、治療選択肢が乏しい状況である。特に再発及び転移を生じた場合に確立した薬物療法もない。しかし、今回の遺伝子変異量解析と免疫チェックポイント分子発現を主たる組織型で解析した結果からは、粘表皮癌(High grade)、唾液腺導管癌、腺癌においては免疫チェックポイント阻害薬による治療介入が有効な可能性が示唆され、治療開発が進まない唾液腺癌に対して免疫チェックポイント阻害薬を用いた臨床研究を推進する根拠となる点で有意義である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 8 results) Book (2 results)

  • [Journal Article] International validation of the revised European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43: Phase IV.2019

    • Author(s)
      Singer S, Amdal CD, Hammerlid E, Tomaszewska IM, Castro Silva J, Mehanna H, Santos M, Inhestern J, Brannan C, Yarom N, Fullerton A, Pinto M, Arraras JI, Kiyota N et al.
    • Journal Title

      Head and Neck

      Volume: 41 Issue: 6 Pages: 1725-1737

    • DOI

      10.1002/hed.25609

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition)2019

    • Author(s)
      Head and Neck Cancer Study Group、Monden N、Asakage T、Kiyota N、Homma A、Matsuura K、Hanai N、Kodaira Ti、Zenda S、Fujii H、Tahara M、Yokota T、Akimoto T、Iwae S、Onitsuka T、Ogawa T、Okano S、Takahashi S、Shimizu Y、Yonezawa K、Hayashi R
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 49 Issue: 7 Pages: 589-595

    • DOI

      10.1093/jjco/hyz052

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age.2019

    • Author(s)
      Saba NF, Blumenschein G Jr, Guigay J, Licitra L, Fayette J, Harrington KJ, Kiyota N, Gillison ML, Ferris RL, Jayaprakash V, Li L, Brossart P.
    • Journal Title

      Oral Oncology

      Volume: 96 Pages: 7-14

    • DOI

      10.1016/j.oraloncology.2019.06.017

    • NAID

      120006716619

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic value of ALDH2 polymorphism for patients with oropharyngeal cancer in a Japanese population2017

    • Author(s)
      Shinomiya Hirotaka、Shinomiya Hitomi、Kubo Mie、Saito Yuki、Yoshida Masafumi、Ando Mizuo、Teshima Masanori、Otsuki Naoki、Kiyota Naomi、Sasaki Ryohei、Nibu Ken-ichi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 12 Pages: e0187992-e0187992

    • DOI

      10.1371/journal.pone.0187992

    • NAID

      120006380399

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 1412017

    • Author(s)
      Kiyota Naomi、Hasegawa Yasuhisa、Takahashi Shunji、Yokota Tomoya、Yen Chia-Jui、Iwae Shigemichi、Shimizu Yasushi、Hong Ruey-Long、Goto Masahiro、Kang Jin-Hyoung、Sum Kenneth Li Wing、Ferris Robert L.、Gillison Maura、Namba Yoshinobu、Monga Manish、Lynch Mark、Tahara Makoto
    • Journal Title

      Oral Oncology

      Volume: 73 Pages: 138-146

    • DOI

      10.1016/j.oraloncology.2017.07.023

    • NAID

      120006377619

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial2017

    • Author(s)
      Kiyota Naomi、Robinson Bruce、Shah Manisha、Hoff Ana O.、Taylor Matthew H.、Li Di、Dutcus Corina E.、Lee Eun Kyung、Kim Sung-Bae、Tahara Makoto
    • Journal Title

      Thyroid

      Volume: - Issue: 9 Pages: 1135-1141

    • DOI

      10.1089/thy.2016.0549

    • NAID

      120006377622

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial2017

    • Author(s)
      Harrington Kevin J、Ferris Robert L、Blumenschein George、Colevas A Dimitrios、Fayette Jerome、Licitra Lisa、Kasper Stefan、Even Caroline、Vokes Everett E、Worden Francis、Saba Nabil F、Kiyota Naomi et al.
    • Journal Title

      The Lancet Oncology

      Volume: 18 Issue: 8 Pages: 1104-1115

    • DOI

      10.1016/s1470-2045(17)30421-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Weekly Low‐Dose Versus Three‐Weekly High‐Dose Cisplatin for Concurrent Chemoradiation in Locoregionally Advanced Non‐Nasopharyngeal Head and Neck Cancer: A Systematic Review and Meta‐Analysis of Aggregate Data2017

    • Author(s)
      Szturz Petr、Wouters Kristien、Kiyota Naomi、Tahara Makoto、Prabhash Kumar、Noronha Vanita、Castro Ana、Licitra Lisa、Adelstein David、Vermorken Jan B.
    • Journal Title

      The Oncologist

      Volume: 22 Issue: 9 Pages: 1056-1066

    • DOI

      10.1634/theoncologist.2017-0015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Japanese Clinical Practice Guideline for Head and Neck Cancer2017

    • Author(s)
      Nibu Ken-ichi、Hayashi Ryuichi、Asakage Takahiro、Nagao Toshitaka、Nakatsuka Takashi
    • Journal Title

      Auris Nasus Larynx

      Volume: 44 Issue: 4 Pages: 375-380

    • DOI

      10.1016/j.anl.2017.02.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lenvatinib for Anaplastic Thyroid Cancer2017

    • Author(s)
      Tahara Makoto、Kiyota Naomi、Yamazaki Tomoko、Chayahara Naoko、Nakano Kenji、Inagaki Lina、Toda Kazuhisa、Enokida Tomohiro、Minami Hironobu、Imamura Yoshinori、Sasaki Tatsuya、Suzuki Takuya、Fujino Katsuki、Dutcus Corina E.、Takahashi Shunji
    • Journal Title

      Frontiers in Oncology

      Volume: 7 Pages: 1-7

    • DOI

      10.3389/fonc.2017.00025

    • NAID

      120006373762

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The EORTC module for quality of life in patients with thyroid cancer: phase III2017

    • Author(s)
      Singer Susanne、Jordan Susan、Locati Laura D、Pinto Monica、Tomaszewska Iwona M、Ara?jo Claudia、Hammerlid Eva、Vidhubala E、Husson Olga、Kiyota Naomi et al
    • Journal Title

      Endocrine-Related Cancer

      Volume: 24 Issue: 4 Pages: 197-207

    • DOI

      10.1530/erc-16-0530

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 頭頸部腫瘍 Up to Date2019

    • Author(s)
      清田尚臣
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Relationship between tumor burden to growth rate and treatment outcomes of nivolumab for patients with head and neck squamous carcinoma.2019

    • Author(s)
      Chiaki Suzuki, Naomi Kiyota, Yoshinori Imamura, Junpei Rikitake, Satoshi Sai, Taiji Koyama, Yasuko Hyogo, Yoshiaki Nagatani, Yohei Funakoshi, Masanori Toyoda, Naoki Otsuki, Ken-ichi Nibu, Hironobu Minami
    • Organizer
      the 2019 ASCO-SITC, Clinical Immuno-Oncology Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Docetaxel plus Cisplatin in Recurrent and/or Metastatic Non-squamous Cell Carcinoma of Head and Neck: a Phase II Trial2018

    • Author(s)
      Yoshinori Imamura*, Naomi Kiyota*, Kaoru Tanaka, Hidetoshi Hayashi, Ichiro Ota, Shigeru Hirano, Shigemichi Iwae, Shujiro Minami, Katsunari Yane, Tomoko Yamazaki, Yoshiaki Nagatani, Masanori Toyoda, Naoki Otuski, Ken-ichi Nibu, and Hironobu Minami
    • Organizer
      第16回日本臨床腫瘍学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Molecular targeted treatment for thyroid cancer2017

    • Author(s)
      Kiyota Naomi
    • Organizer
      2nd Congress of Asia-Pacific Society of Thyroid Surgery
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 転移再発甲状腺がんに対する薬物療法2017

    • Author(s)
      清田尚臣
    • Organizer
      日本内分泌外科学会2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 頭頸部がんに対する免疫チェックポイント阻害薬の適正使用2017

    • Author(s)
      清田尚臣
    • Organizer
      第31回日本耳鼻咽喉科学会専門医講習会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 頭頸部がんに対する分子標的薬及び免疫チェックポイント阻害薬の役割2017

    • Author(s)
      清田尚臣
    • Organizer
      第69回日本気管食道科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 口腔癌に対する免疫チェックポイント阻害薬の適正使用と腫瘍内科医との診療連携2017

    • Author(s)
      清田尚臣
    • Organizer
      第36回日本口腔腫瘍学会総会学術大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 腫瘍内科医からみた頭頸部がん臨床試験におけるIMRTの重要性と課題2017

    • Author(s)
      清田尚臣
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 頭頸部がんに対する免疫チェックポイント阻害薬2017

    • Author(s)
      清田尚臣
    • Organizer
      日本頭頸部癌学会主催第8回教育セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 頭頸部癌診療ガイドライン 2018年版(第3版)2017

    • Author(s)
      日本頭頸部癌学会
    • Total Pages
      192
    • Publisher
      金原出版
    • ISBN
      9784307203791
    • Related Report
      2017 Research-status Report
  • [Book] 頭頸部がん薬物療法ハンドブック2017

    • Author(s)
      清田 尚臣、田原 信、藤井 正人
    • Total Pages
      232
    • Publisher
      中外医学社
    • ISBN
      9784498062696
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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