Immune escape mediated by the EGFR-derived signal: From Mechanism to Therapy

• Project/Area Number: 15K09237
• 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: Iwate Medical University (2017); Miyagi Prefectural Hospital Organization Miyagi Cancer Center (2015-2016)
• Principal Investigator: Mamondo Makoto 岩手医科大学, 医学部, 教授 (40344676)
• Co-Investigator(Kenkyū-buntansha): 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 非小細胞肺癌 / EGFR / 分子細胞腫瘍学 / 肺癌 / モデルマウス / 分子細胞呼吸器学 / 免疫チェックポイント

Outline of Final Research Achievements

Immune checkpoint inhibitors targeting PD-L1 and PD-1 often show synergistic effects on NSCLCs. To elucidate the role of EGFR-mediated signal on lung tumor immunology, LLC cells were examined for the immune modulator expression. Although LAG-3 and B7-H3 expression was negative, a fair amount of PD-L1 was detected. We then established PD-L1 knockout cells and implanted into syngeneic mice, but TIL infiltration was relatively low. To increase TIL infiltration we introduced CTIIA, and succeeded in MHC up-regulation.

Research Products

• [Journal Article] Deficiency of protein-L-isoaspartate (D-aspartate) <i>O</i>-methyl-transferase expression under endoplasmic reticulum stress promotes epithelial mesenchymal transition in lung adenocarcinoma (2018)
  • Author(s): Yamashita Masahiro、Ogasawara Masahito、Kawasaki Yasushi、Niisato Miyuki、Saito Heisuke、Kasai Shuya、Maesawa Chihaya、Maemondo Makoto、Yamauchi Kohei
  • Journal Title: Oncotarget Volume: 9 Issue: 17 Pages: 13287-13300
  • DOI: 10.18632/oncotarget.24324
  • Peer Reviewed / Open Access
• [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 Issue: 3 Pages: 355-367
  • DOI: 10.1016/j.ccell.2018.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations. (2018)
  • Author(s): Oizumi S, Sugawara S, Minato K, Harada T, Inoue A, Fujita Y, Maemondo M, Watanabe S, Ito K, Gemma A, Demura Y, Fukumoto S, Isobe H, Kinoshita I, Morita S, Kobayashi K, Hagiwara K, Aiba K, Nukiwa T.
  • Journal Title: ESMO Open Volume: 3(2) Issue: 2 Pages: e000313-e000313
  • DOI: 10.1136/esmoopen-2017-000313
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias (2018)
  • Author(s): Yamashita M, Saito R, Yasuhira S, Fukuda Y, Sasamo H, Sugai T, Yamauchi K, Maemondo M
  • Journal Title: J Immunol Res Volume: 2018 Pages: 1436236-1436236
  • DOI: 10.1155/2018/1436236
  • Peer Reviewed / Open Access
• [Journal Article] Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer) (2017)
  • Author(s): Nokihara H
  • Journal Title: Ann Oncol Volume: 28 Issue: 11 Pages: 2698-2706
  • DOI: 10.1093/annonc/mdx419
  • Peer Reviewed
• [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: 1-6
  • DOI: 10.1155/2016/5297329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Randomized phase II trial comparing amrubicin with re-challenge of platinum doublet in patients with sensitive-relapsed small-cell lung cancer: North Japan Lung Cancer Study Group trial 0702 (2015)
  • Author(s): .Inoue A, Sugawara S, Maemondo M, Mori Y, Oizumi S, Harada M, Taima K, Morikawa N, Ishida T, Kinoshita I, Watanabe H, Suzuki T, Nakagawa T, Saito R, Nukiwa T
  • Journal Title: Lung Cancer Volume: 89 Issue: 1 Pages: 61-5
  • DOI: 10.1016/j.lungcan.2015.04.012
  • Peer Reviewed
• [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis. (2015)
  • Author(s): Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
  • Journal Title: Cancer Lett. Volume: 365 Issue: 2 Pages: 223-228
  • DOI: 10.1016/j.canlet.2015.05.022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Factors associated with a poor response to gefitinib in the NEJ002 study: Smoking and the L858R mutation. (2015)
  • Author(s): Fukuhara T, Yoshizawa H et al.
  • Journal Title: Lung Cancer Volume: 88 Issue: 2 Pages: 181-6
  • DOI: 10.1016/j.lungcan.2015.02.004
  • Peer Reviewed / Open Access
• [Journal Article] The role of smoking status on the progression-free survival of non-small-cell lung cancer patients harboring activating epidermal growth factor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor: a meta-analysis of prospective randomized trials. (2015)
  • Author(s): Hasegawa Y, Ando M, Maemondo M, Yamamoto S, Isa S, Saka H, Kubo A, Kawaguchi T, Takada M, Rosell R, Kurata T, Ou SH.
  • Journal Title: The Oncologist Volume: 20 Issue: 3 Pages: 1-9
  • DOI: 10.1634/theoncologist.2014-0285
  • Peer Reviewed
• [Presentation] alectinib耐性後にc-Met遺伝子増幅を来しcrizotinibが奏効したALK融合遺伝子陽性肺腺癌の一例, (2015)
  • Author(s): 渡邉香奈、突田容子、盛田麻美、鈴木綾、福原達朗、玉井恵一、片山量平、前門戸任
  • Organizer: 第５６回日本肺癌学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-11-26
• [Presentation] 高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定 (2015)
  • Author(s): 渡邉香奈、福原達郎、突田容子、盛田麻美、鈴木綾、寺崎浩司、前門戸任
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17