Genetic alterations and expressions of immune check point molecules in sinonasal neuroendocrine carcinoma

• Project/Area Number: 20K09731
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kobe 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): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 鼻副鼻腔神経内分泌腫瘍 / 嗅神経芽細胞腫 / 次世代シーケンサー / 腫瘍免疫微小環境 / 腫瘍遺伝子変異量 / がん免疫微小環境 / 免疫チェックポイント分子 / 遺伝子変異 / 鼻副鼻腔悪性腫瘍 / 免疫多重染色 / 頭頸部がん / 神経内分泌悪性腫瘍 / 遺伝子変化

Outline of Research at the Start

本研究において希少疾患である鼻副鼻腔神経内分泌悪性腫瘍における特徴的な遺伝子変化を解析し、多重免疫組織染色を用いた腫瘍細胞及び腫瘍周囲細胞における免疫チェックポイント分子発現を解析することで、本希少疾患の診断及び治療法の開発につなげるデータを収集する。

Outline of Final Research Achievements

Olfactory neuroblastoma is one of the rare head and neck malignancies. There have been scarce data about genetic variant, tumor mutational burden (TMB) and tumor immune microenvironment (TIME) of ONB. This research elucidated genetic variants and frequency of TMB-High by Oncomine tumor mutational load assay and also explored the TIME of ONB by multiplex fluorescent immunohistochemistry.

Academic Significance and Societal Importance of the Research Achievements

ONBは希少がんであり小さな研究成果の蓄積が病態の解明や治療法の開発につながる。このため、本研究結果から免疫チェックポイント阻害薬を始めとするがん免疫療法の臨床応用の可能性について新たな知見が得られたことは学術的にも社会的にも意義がある。

Research Products

• [Journal Article] Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651 (2023)
  • Author(s): Haddad R、Harrington K、Tahara M、Ferris RL、Gillison M、Fayette J、Daste A、Koralewski P、Zurawski B、Taberna M、Saba NF、Mak M、Kawecki A、Girotto G、Alvarez A、Even C、Toledo J、Guminski A、Muller-Richter U、Kiyota N、Roberts M、Khan T、Miller-Moslin K、Wei L、Argiris A
  • Journal Title: Journal of Clinical Oncology Volume: 41 Issue: 12 Pages: 2166-2180
  • DOI: 10.1200/jco.22.00332
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial (2022)
  • Author(s): Satoshi Okumura, Mikiya Ishihara, Naomi Kiyota, Kimikazu Yakushijin, Kohichi Takada, Shinichiro Kobayashi, Hiroaki Ikeda, Makoto Endo, Koji Kato, Shigehisa Kitano, Akihiko Matsumine, Yasuhiro Nagata,...Hiroshi Shiku
  • Journal Title: BMJ Open Volume: 12(11) Issue: 11 Pages: e065109-e065109
  • DOI: 10.1136/bmjopen-2022-065109
  • Peer Reviewed / Open Access
• [Journal Article] Long-term Outcomes with Nivolumab as First-line Treatment in Recurrent or Metastatic Head and Neck Cancer: Subgroup Analysis of CheckMate 141 (2022)
  • Author(s): Gillison ML、Blumenschein G、Fayette J、Guigay J、Colevas D、Licitra L、Harrington KJ、Kasper S、Vokes EE、Even C、Worden F、Saba NF、Iglesias D、Haddad R、Rordorf T、Kiyota N、Tahara M、Jayaprakash V、Wei L、Ferris RL
  • Journal Title: The Oncologist Volume: 27 Issue: 2 Pages: e194-e198
  • DOI: 10.1093/oncolo/oyab036
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transition of the PD?1 occupancy of nivolumab on T cells after discontinuation and response of nivolumab re?challenge (2022)
  • Author(s): Nose Taku、Funakoshi Yohei、Suto Hirotaka、Nagatani Yoshiaki、Imamura Yoshinori、Toyoda Masanori、Kiyota Naomi、Minami Hironobu
  • Journal Title: Molecular and Clinical Oncology Volume: 16 Issue: 5
  • DOI: 10.3892/mco.2022.2537
  • Peer Reviewed
• [Journal Article] Systemic therapy for salivary gland malignancy: current status and future perspectives (2022)
  • Author(s): Imamura Yoshinori、Kiyota Naomi、Tahara Makoto、Hanai Nobuhiro、Asakage Takahiro、Matsuura Kazuto、Ota Ichiro、Saito Yuki、Sano Daisuke、Kodaira Takeshi、Motegi Atsushi、Yasuda Koichi、Takahashi Shunji、Yokota Tomoya、Okano Susumu、Tanaka Kaoru、Onoe Takuma、Ariizumi Yosuke、Homma Akihiro
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 52 Issue: 4 Pages: 293-302
  • DOI: 10.1093/jjco/hyac008
  • Peer Reviewed
• [Journal Article] Roles of skull base surgery and particle radiotherapy for orbital malignant tumors involving the skull base (2021)
  • Author(s): Teshima Masanori、Shinomiya Hirotaka、Kimura Hidehito、Hashikawa Kazunobu、Kiyota Naomi、Miyawaki Daisuke、Sasaki Ryohei、Kohmura Eiji、Nibu Ken‐ichi
  • Journal Title: Laryngoscope Investigative Otolaryngology Volume: 6 Issue: 6 Pages: 1347-1352
  • DOI: 10.1002/lio2.687
  • NAID: 120007179199
  • Peer Reviewed / Open Access
• [Journal Article] Microsatellite instability-high colorectal cancer patient-derived xenograft models for cancer immunity research (2021)
  • Author(s): Funakoshi Yohei、Suto Hirotaka、Nagatani Yoshiaki、Imamura Yoshinori、Toyoda Masanori、Kiyota Naomi、Matsumoto Hisayuki、Tanaka Shinwa、Takai Ryo、Hasegawa Hiroshi、Yamashita Kimihiro、Matsuda Takeru、Kakeji Yoshihiro、Minami Hironobu
  • Journal Title: Journal of Cancer Research and Therapeutics Volume: 17 Issue: 6 Pages: 1358-1358
  • DOI: 10.4103/jcrt.jcrt_1092_20
  • Peer Reviewed / Open Access
• [Journal Article] Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial (2021)
  • Author(s): Imamura Yoshinori、Tanaka Kaoru、Kiyota Naomi、Hayashi Hidetoshi、Ota Ichiro、Arai Akihito、Iwae Shigemichi、Minami Shujiro、Yane Katsunari、Yamazaki Tomoko、Nagatani Yoshiaki、Toyoda Masanori、Takahama Takayuki、Sakai Kazuko、Nishio Kazuto、Otsuki Naoki、Nibu Ken-ichi、Minami Hironobu
  • Journal Title: Medical Oncology Volume: 38 Issue: 11
  • DOI: 10.1007/s12032-021-01581-z
  • NAID: 120007159886
  • Peer Reviewed
• [Journal Article] Immunosuppressive effects and mechanisms of three myeloid-derived suppressor cells subsets including monocytic-myeloid-derived suppressor cells, granulocytic-myeloid-derived suppressor cells, and immature-myeloid-derived suppressor cells (2021)
  • Author(s): Funakoshi Yohei、Nagatani Yoshiaki、Suto Hirotaka、Imamura Yoshinori、Toyoda Masanori、Kiyota Naomi、Yamashita Kimihiro、Minami Hironobu
  • Journal Title: Journal of Cancer Research and Therapeutics Volume: 17 Issue: 4 Pages: 1093-1093
  • DOI: 10.4103/jcrt.jcrt_1222_20
  • Peer Reviewed / Open Access
• [Journal Article] Real-world safety and effectiveness of nivolumab for recurrent or metastatic head and neck cancer in Japan: a post-marketing surveillance (2021)
  • Author(s): Tahara Makoto、Kiyota Naomi、Nibu Ken-ichi、Akamatsu Ayumi、Hoshino Tomohiro、Hayashi Ryuichi
  • Journal Title: International Journal of Clinical Oncology Volume: 26 Issue: 9 Pages: 1619-1627
  • DOI: 10.1007/s10147-021-01949-1
  • Peer Reviewed / Open Access