Analyzation of anticancer drug resistance mechanism focusing on macrophage related molecules in renal cancer

• Project/Area Number: 16K11013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kumamoto University
• Principal Investigator: Motoshima Takaonobu 熊本大学, 大学院生命科学研究部(医), 助教 (60726355)
• Co-Investigator(Kenkyū-buntansha): 河野 吉昭 熊本大学, 大学院生命科学研究部(医), 講師 (30593793) ; 菰原 義弘 熊本大学, 大学院生命科学研究部(医), 准教授 (40449921)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎細胞癌 / 癌免疫 / マクロファージ / TIMD4 / 免疫療法 / 腎癌

Outline of Final Research Achievements

We tested if TAM or TAM-rated molecules would be associate clinicopathological factors or cancer progression. PD-L1 expression in papillary RCC was detected, however, no significant correlation with clinicopathological factors were seen. This study was first report described the PD-L1 expression in papillary RCC. TIMD4 and CD163-positive cancer cells were observed in clear cell RCC, and positive cases showed poor clinical course. TIMD4 was suggested to be involved in chemo-resistance by means of in vitro study using RCC cell lines. TAM phenotype between primary RCC and metastatic RCC was tested, and M1-like TAMs were suggested to be increased in metastatic site.

Academic Significance and Societal Importance of the Research Achievements

腎癌においてTAMあるいはTAM関連分子の重要性を明らかにした。予後予測因子やあらたな治療法開発につながるように今後も研究を続けていきたい。

Research Products

• [Journal Article] CD163-positive cancer cells are potentially associated with high malignant potential in clear cell renal cell carcinoma (2018)
  • Author(s): Ma Chaoya、Horlad Hasita、Ohnishi Koji、Nakagawa Takenobu、Yamada Sohsuke、Kitada Shohei、Motoshima Takanobu、Kamba Tomomi、Nakayama Toshiyuki、Fujimoto Naohiro、Takeya Motohiro、Komohara Yoshihiro
  • Journal Title: Medical Molecular Morphology Volume: 51 Issue: 1 Pages: 13-20
  • DOI: 10.1007/s00795-017-0165-8
  • Peer Reviewed
• [Journal Article] Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma (2018)
  • Author(s): Motoshima Takanobu、Miura Yuji、Wakigami Nanako、Kusada Natsuki、Takano Toshimi、Inoshita Naoko、Okaneya Toshikazu、Sugiyama Yutaka、Kamba Tomomi、Takeya Motohiro、Komohara Yoshihiro
  • Journal Title: Medical Molecular Morphology Volume: 51 Issue: 1 Pages: 57-63
  • DOI: 10.1007/s00795-017-0174-7
  • Peer Reviewed
• [Journal Article] Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma. (2018)
  • Author(s): 1.Motoshima T, Miura Y, Wakagami N, Kusada N, Takano T, Inoshita N, Okaneya T, Sugiyama Y, Kamba T, Takeya M, Komohara Y
  • Journal Title: Med Mol Morphol. Volume: 51 Pages: 57-63
  • Peer Reviewed / Open Access
• [Journal Article] Contrasting effects of cyclophosphamide onanti-CTL-associated protein 4 blockade therapy intwo mouse tumor models. (2017)
  • Author(s): 2.Yuichi Iida, Nanae Harashima, Takanobu Motoshima, Yoshihiro Komohara, Masatoshi Eto and Mamoru Harada.
  • Journal Title: Cancer Sci Volume: 108 Pages: 1974-1984
  • Peer Reviewed / Open Access
• [Journal Article] The significance of TIMD4 expression in clear cell renal carcinoma. (2017)
  • Author(s): 3.Hiromu Yano, Takanobu Motoshima, Chaoya Ma, Cheng Pan, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Naohiro Fujimoto, Tomomi Kamba, Motohiro Takeya, Yoshihiro Komohara.
  • Journal Title: Med Mol Morphol Volume: 50 Pages: 220-226
  • Peer Reviewed / Open Access
• [Journal Article] PD-L1 expression in papillary renal cell carcinoma (2017)
  • Author(s): Takanobu Motoshima, Yoshihiro KomoharaEmail author, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda and Masatoshi Eto
  • Journal Title: BMC Urology Volume: 17 Issue: 1 Pages: 8-8
  • DOI: 10.1186/s12894-016-0195-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Characterization of chimeric TFE3 transcription factors found in Xp11.2 translocation renal cell carcinoma (2018)
  • Author(s): Takanobu Motoshima, Yorifumi Satou, Paola Miyazato, Hisashi Hasumi, Ying Huang, Tsuyoshi Kadomatsu, Masahiro Yao, Yoji Nagashima, Mitsuko Furuya, Yuchi Oike, Laura S Schmidt, Tomomi Kamba, W Marston Linehan, Masaya Baba
  • Organizer: アメリカ泌尿器科学会
  • Int'l Joint Research
• [Presentation] 熊本大学におけるロボット支援下腎部分切除術（RAPN）の初期経験 (2018)
  • Author(s): 元島 崇信、矢津田旬二、村上洋嗣、山口隆大、田上憲一郎、杉山豊、神波大己
  • Organizer: 第49回腎癌研究会
• [Presentation] RAPNにおけるRENAL nephrometry scoreの意義 (2018)
  • Author(s): 元島 崇信、福島結美、矢津田旬二、村上洋嗣、山口隆大、田上憲一郎、神波大己
  • Organizer: 第32回泌尿器内視鏡学会
• [Presentation] 神経内分泌腫瘍（NET:neuroendocrine tumor）と診断された2症例 (2018)
  • Author(s): 元島 崇信, 林 英孝, 福島 結美, 田上憲一郎, 神波大己
  • Organizer: 日本泌尿器科学会 第197回熊本地方会
• [Presentation] 進行性腎癌に対するNivolumab(Opdivo)投与の初期経験 (2018)
  • Author(s): 元島 崇信、福島結美、矢津田旬二、村上洋嗣、山口隆大、田上憲一郎、 杉山豊、神波大己
  • Organizer: 第56回日本癌治療学会
• [Presentation] 去勢抵抗性前立腺癌に対する10コース以上ドセタキセルを投与した症例の検討 (2018)
  • Author(s): 元島崇信、上園英太、山口隆大、神波大己
  • Organizer: 第106回日本泌尿器科学会総会
• [Presentation] TFE3活性化腎細胞癌の診断補助マーカーの探索と評価 (2017)
  • Author(s): 元島崇信,馬場理也,蓮見壽史,加藤生真,長嶋洋治,黒田直人,高橋 渡,河野吉昭,矢尾正祐,江藤正俊,古屋充子,神波大己
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] Xp11転座型腎癌と診断された2症例のレトロスペクティブな解析 (2017)
  • Author(s): 元島 崇信,西澤 秀和,馬場 理也,古谷 充子,加藤 生真,神波 大己
  • Organizer: 第48回腎癌研究会
• [Presentation] TFE-3染色で陽性と診断された腎癌3症例のレトロスペクティブな解析 (2017)
  • Author(s): 元島 崇信,西澤 秀和,馬場 理也,古谷 充子,加藤 生真,神波 大己
  • Organizer: 第55回日本癌治療学会
• [Presentation] Characterization of chimeric TFE3 transcription factors found in Xp11.2 translocation renal cell carcinoma (2017)
  • Author(s): 元島崇信, 馬場理也,蓮見壽史, 黄瑩,佐藤賢文,宮里パオラ,門松 毅 矢尾正祐,長嶋洋治,古屋充子,尾池雄一,神波大己,Laura S Schmidt, W Marston Linehan
  • Organizer: 第76回日本癌学会
• [Presentation] 熊本大学における進行性前立腺癌に対するドセタキセル治療成績の検討 (2017)
  • Author(s): 元島 崇信、上園 英太、山口 隆大、神波 大己
  • Organizer: 第33回前立腺癌シンポジウム
• [Presentation] PD-L1/B7-H1 expression in papillary renal cell carcinoma (2017)
  • Author(s): Takanobu Motoshima, Yoshihiro KomoharaEmail author, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda and Masatoshi Eto
  • Organizer: Advanced in Urology 2017
  • Place of Presentation: San Diego
• [Presentation] PD-L1 and PD-L2 expression in papillary renal cell carcinoma (2016)
  • Author(s): Takanobu Motoshima, Yoshihiro KomoharaEmail author, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda and Masatoshi Eto
  • Organizer: 第75回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] 乳頭状腎細胞癌におけるPD-L1発現についての検討 (2016)
  • Author(s): 元島崇信、菰原義弘、野口紘嗣、山田壮亮、北田昇平、中山敏幸、竹屋元裕、江藤正俊
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台
• [Presentation] PD-L1 and PD-L2 expression in papillary renal cell carcinoma (2016)
  • Author(s): Takanobu Motoshima, Yoshihiro KomoharaEmail author, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda and Masatoshi Eto
  • Organizer: 第2回日本泌尿器腫瘍学会
  • Place of Presentation: 横浜
• [Presentation] 乳頭状腎細胞癌におけるPD-L1 発現についての検討 (2016)
  • Author(s): 元島崇信、菰原義弘、野口紘嗣、山田壮亮、北田昇平、中山敏幸、竹屋元裕、江藤正俊
  • Organizer: 第68回西日本泌尿器科学会総会
  • Place of Presentation: 下関