Tumor associated Neutrophils control NSCLC-Immune interface

• Project/Area Number: 16K09597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: FUKUHARA TATSURO 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 特任研究員 (80400365)
• Co-Investigator(Kenkyū-buntansha): 前門戸 任 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 特任研究員 (40344676) ; 田中 伸幸 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 部長 (60280872) ; 長島 隆一 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 研究技師 (20783707)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 非小細胞肺がん / 好中球 / 癌 / 非小細胞肺癌 / 肺癌 / EGFR / 抗腫瘍免疫

Outline of Final Research Achievements

NSCLC is one of the most common cancer worldwide and therapy-resistance awaits further improvement. We found that syngeneic lung tumor includes a Neutrophil population. To study a role of tumor associated Neutrophil (TAN), we depleted Neutrophil in vivo. Neutrophil depletion decreased tumor size, which prompted us to screen for a factor that recruits Neutrophils into NSCLC. We identified S100A proteins are abundantly expressed in NSCLC. S100A protein expressions were induced in response to EGF. Because former reports suggested their potential ability to recruit Neutrophils, S100A may be a good marker for NSCLC as well as a potential therapeutic targets.

Academic Significance and Societal Importance of the Research Achievements

非小細胞肺癌における腫瘍内好中球の意義を見出したことが学術的意義がある。新たな肺癌マーカー遺伝子を発見した点で社会的意義がある。肺癌の治療標的としての可能性があり発展すれば、社会貢献となることが期待される。

Research Products

• [Journal Article] Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial (2019)
  • Author(s): Saito Haruhiro、Fukuhara Tatsuro、Maemondo Makotoら
  • Journal Title: The Lancet Oncology Volume: 20 Pages: 625-635
  • DOI: 10.1016/s1470-2045(19)30035-x
  • Peer Reviewed
• [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth. (2018)
  • Author(s): M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
  • Journal Title: Cancer Cell Volume: 12 Pages: 355-367
  • DOI: 10.1016/j.ccell.2018.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relapsed Myasthenia Gravis after Nivolumab Treatment (2018)
  • Author(s): Mitsune Ayumi、Yanagisawa Satoru、Fukuhara Tatsuro、Miyauchi Eisaku、Morita Mami、Ono Manabu、Tojo Yutaka、Ichinose Masakazu
  • Journal Title: Intern. Med. Volume: 9153 Issue: 13 Pages: 1893-1897
  • DOI: 10.2169/internalmedicine.9153-17
  • NAID: 130007387159
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] EGFR Mutation Analysis of Circulating Tumor DNA Using an Improved PNA-LNA PCR Clamp Method (2016)
  • Author(s): Watanabe K, Fukuhara T, Tsukita Y, Morita M, Suzuki A, Tanaka N, Terasaki H, Nukiwa T, Maemondo M
  • Journal Title: Can Respir J. Volume: 5297329 Pages: 5297329-5297329
  • DOI: 10.1155/2016/5297329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Updated survival outcomes of NEJ005/TCOG0902, a randomized PII of gefitinid and chemotherapy in EGFR-mutant NSCLC (2017)
  • Author(s): Tatsuro Fukuhara, Satoshi Oizumi, Shunichi Sugawara, Koichi Minato, Toshiyuki Harada, Akira Inoueら
  • Organizer: 18th World Conference on Lung Cancer
  • Int'l Joint Research