Immunoescape from innnate/adoptive antitumor immunity via EGF family receptor in non-small cell lung cancer

• Project/Area Number: 25462189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: Okita Riki 川崎医科大学, 医学部, 講師 (90467762)
• Co-Investigator(Kenkyū-buntansha): NAKATA Masao 川崎医科大学, 医学部, 教授 (30368641)
• Research Collaborator: Kiessling Rolf カロリンスカ研究所, 教授
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍免疫 / 非小細胞肺癌 / 悪性胸膜中皮腫 / NK細胞 / EGFR / HER2 / NKG2Dリガンド / NK細胞傷害活性 / 癌免疫療法 / 肺癌 / NK cell / NKG2D ligand / lung cancer

Outline of Final Research Achievements

We reported following findings. 1: EGFR/PI3K-AKT signaling regulates the expression of NKG2D ligands MICB via miR20a, resulted in enhanced NK cell-mediated cytotoxicity against non-small cell lung cancer cells. 2: Overexpression of MICA/B is independent improved prognostic factor for patients with non-small cell lung cancer. 3: EGFR/HER2 dual tyrosine kinase inhibitor lapatinib upregulates HER2, resulted in enhanced antibody dependent cellular cytotoxicity with NK cells in malignant mesothelioma cell lines.

Research Products

• [Int'l Joint Research] Karolinska Institutet(Sweden)
• [Int'l Joint Research] Martin Luther University(Germany)
• [Journal Article] MHC class I chain‑related molecule A and B expression is upregulated by cisplatin and associated with good prognosis in patients with non‑small cell lung cancer (2016)
  • Author(s): Riki Okita1, Takuro Yukawa, Yuji Nojima, Ai Maeda, Shinsuke Saisho, Katsuhiko Shimizu, Masao Nakata
  • Journal Title: Cancer Immunol Immunother Volume: 65 Issue: 5 Pages: 499-509
  • DOI: 10.1007/s00262-016-1814-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Contrasting effects of the cytotoxic anticancer drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on NK cell-mediated cytotoxicity via regulation of NKG2D ligand in non-small-cell lung cancer cells. (2015)
  • Author(s): Okita R, Wolf D, Yasuda K, Maeda A, Yukawa T, Saisho S, Shimizu K, Yamaguchi Y, Oka M, Nakayama E, Lundqvist A, Kiessling R, Seliger B, Nakata M.
  • Journal Title: PLoS One Volume: 10 Issue: 10 Pages: e0139809-e0139809
  • DOI: 10.1371/journal.pone.0139809
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity via upregulation of HER2 in malignant mesothelioma cells (2015)
  • Author(s): Riki Okita , Katsuhiko Shimizu, Yuji Nojima, Takuro Yukawa, Ai Maeda, Shinsuke Saisho, Masao Nakata.
  • Journal Title: Oncology Reports Volume: 34 Issue: 6 Pages: 2864-2870
  • DOI: 10.3892/or.2015.4314
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Overexpression of NK cell-activating ligand MICA/B correlates with superior outcomes and might be a therapeutic target for chemoimmunotherapy in non-small-cell lung cancer. (2015)
  • Author(s): Riki Okita, Takuro Yukawa, Yuji Nojima, Ai Maeda, Shinsuke Saisho, Katsuhiko Shimizu, Masao Nakata
  • Organizer: ESMO Asia 2015
  • Place of Presentation: Singapore, Singapore
  • Year and Date: 2015-12-19
  • Int'l Joint Research
• [Presentation] 非小細胞肺癌におけるNKG2DリガンドMICA/B発現の意義：切除例における予後との関連ならびにシスプラチンによるMICA/B発現誘導効果に関する検討 (2015)
  • Author(s): 沖田理貴、湯川拓郎、野島雄史、前田 愛、最相晋輔、清水克彦、中田昌男
  • Organizer: 第28回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 川越東武ホテル、川越市、埼玉県
  • Year and Date: 2015-12-03
• [Presentation] 悪性胸膜中皮腫細胞においてlapatinibはtrastuzumabの抗体依存性細胞傷害活性を増強する (2015)
  • Author(s): 沖田理貴、野島雄史、前田 愛、最相晋輔、清水克彦、中田昌男
  • Organizer: 第6回 Japan Mesothelioma Interest Group 研究会
  • Place of Presentation: 北九州国際会議場、北九州市、福岡県
  • Year and Date: 2015-11-14
• [Presentation] Lapatinib enhances trastuzumab-mediated antibody-dependent cellular cytotoxicity by upregulating HER2 in malignant pleural mesothelioma cells. (2015)
  • Author(s): Riki Okita, Shinji Nojima, Ai Maeda, Takuro Yukawa, Shinsuke Saisho, Katsuhiko Shimizu, Masao Nakata.
  • Organizer: The 2015 European Cancer Congress
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-09-28
  • Int'l Joint Research
• [Presentation] 化学療法前後における非小細胞肺癌細胞のNKG2Dリガンド発現解析 (2015)
  • Author(s): 沖田理貴, 保田紘一郎, 前田 愛, 湯川拓郎, 最相晋輔, 清水克彦, 中田昌男
  • Organizer: 第32回日本呼吸器外科学会総会
  • Place of Presentation: サンポートホール高松、高松市、香川県
  • Year and Date: 2015-05-15
• [Presentation] Anticancer drugs effect on NK cell-mediated cytotoxicity via the regulation of NKG2D ligand expression in non-small cell lung cancer cells (2013)
  • Author(s): Okita R, Nojima Y, Yasuda K, Maeda A, Yukawa T, Saisho S, Hirami Y, Shimizu K, Nakata M
  • Organizer: European Cancer Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] 非小細胞肺癌細胞において抗腫瘍薬がNK細胞傷害活性に与える影響の解析 (2013)
  • Author(s): 沖田理貴、野島雄史、保田紘一郎、前田 愛、湯川拓郎、最相晋輔、清水克彦、中田昌男
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] EGFR signaling effects on NK cell-mediated cytotoxicity via NKG2D ligands-NKG2D interaction in non-small cell lung cancer cells (2013)
  • Author(s): Okita R, Nojima Y, Yasuda K, Maeda A, Yukawa T, Saisho S, Hirami Y, Shimizu K, Nakata M
  • Organizer: 15th World Conference on Lung Cancer
  • Place of Presentation: Sydney, Australia
• [Remarks] 川崎医科大学呼吸器外科学教室 研究紹介
  • URL: http://www.kawasaki-m.ac.jp/gts/07-01.html
• [Remarks] Karolinska Institutet, Rolf Kiessling's Group
  • URL: http://ki.se/en/onkpat/rolf-kiesslings-group