Comparative immunological research on tumor-associated immune cells using Drosophila

• Project/Area Number: 18K19395
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Nakanishi Yoshinobu 金沢大学, 薬学系, 特任教授 (40172358)
• Co-Investigator(Kenkyū-buntansha): 白土 明子 札幌医科大学, 医療人育成センター, 教授 (90303297) ; 永長 一茂 弘前大学, 地域戦略研究所, 准教授 (70401891)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 癌 / 自然免疫 / 腫瘍随伴免疫細胞 / 貪食 / アポトーシス / ショウジョウバエ / 食細胞 / 免疫細胞

Outline of Final Research Achievements

Some types of immune cells in mammals help cancer cells and are called tumor-associated immune cells. In the present study, we verified the possible existence of such immune cells in Drosophila. If the answer is positive, studying tumor-associated immune cells with the aid of genetic approach is made possible.
Establishing a Drosophila model of cancer, we first examined the distribution of hemocytes in the vicinity of cancer cells, but this was not the case. We next examined the effects of inhibition of phagocytic activities of immune cells on cancer development, but the data showed an increase, not decrease, of the incident of cancer. Finally, we determined the pattern of gene expression in immune cells isolated from cancer-bearing and normal Drosophila. We found a clear difference in mRNA repertoire between the two groups. This change was toward a decline of immune cells’ activity. Collectively, our study suggests the presence of tumor-associated immune cells in Drosophila.

Academic Significance and Societal Importance of the Research Achievements

学術的意義：ヒトを含めた哺乳類で存在が示された腫瘍随伴免疫細胞については不明な点が多く残されている。ショウジョウバエは遺伝学を駆使できるモデル生物であり、今後は腫瘍随伴免疫細胞を遺伝学的に解析することが可能となる。その結果、腫瘍随伴免疫細胞の発生や機能発揮に必要な遺伝子群の網羅的な同定が行われて、研究が大きく進展すると期待される。
社会的意義：腫瘍随伴免疫細胞の理解が進めば、この種の免疫細胞の量や質を人工的に改変するなどの、癌を予防・治療するための新たな医療の開発につながると期待される。

Research Products

• [Int'l Joint Research] Hasanuddin University(インドネシア)
• [Journal Article] Fruit fly as a model organism in the study of human diseases and drug discovery (2019)
  • Author(s): Nainu F, Nakanishi Y & Shiratsuchi A
  • Journal Title: 札幌医科大学医療人育成センター紀要 = Journal of center for medical education Sapporo Medical University = Journal of center for medical education Sapporo Medical University Volume: 10 Pages: 21-32
  • DOI: 10.15114/jcme.10.21
  • NAID: 120006647837
  • URL: https://sapmed.repo.nii.ac.jp/records/14061
  • Year and Date: 2019-03-31
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory effects of viral infection on cancer development (2019)
  • Author(s): Rahmatika Dini、Kuroda Nanae、Min Zhang、Nainu Firzan、Nagaosa Kaz、Nakanishi Yoshinobu
  • Journal Title: Virology Volume: 528 Pages: 48-53
  • DOI: 10.1016/j.virol.2018.12.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transcription repressor-mediated control of engulfment receptor expression in Drosophila phagocytes. (2019)
  • Author(s): Nonaka, S., Sono, M., Hoshi, C., Kanetani, T., Nakayama, H., Dohmae, N., and Nakanishi, Y.
  • Journal Title: Experimental Cell Research Volume: 381 Issue: 1 Pages: 10-17
  • DOI: 10.1016/j.yexcr.2019.04.032
  • Peer Reviewed
• [Journal Article] ショウジョウバエを用いた食品の機能性研究 (2019)
  • Author(s): 永長一茂, 中井雄治
  • Journal Title: 日本家政学会誌 Volume: 70 Pages: 770-777
  • NAID: 130007749744
• [Presentation] The effects of tobacco components on gene expression of E. coli (2019)
  • Author(s): Shiratsuchi, A., Ariki, S., Kidoura, Y., Hasegawa, H., and Nakanishi, Y.
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Regulation of bacterial virulence by mixed bacterial culture in the host (2019)
  • Author(s): A. Shiratsuchi
  • Organizer: ウメア大学歯学部セミナー
  • Int'l Joint Research / Invited
• [Presentation] Regulation of bacterial virulence in infectious condition (2019)
  • Author(s): A. Shiratsuchi
  • Organizer: Symposium of the European Network for Aggregatibacter actinomycetemcomitans Research
  • Int'l Joint Research / Invited
• [Presentation] Regulation of virulence of Escherichia coli in host organism：宿主感染時の大腸菌の毒性抑 (2019)
  • Author(s): Shiratsuchi, A., Yamashita, S., Amagasa,Y., Komiyama, C., Narita, T., Yamamoto, K., Ishihama, A., and Nakanishi, Y.
  • Organizer: 第92回生化学会大会
• [Presentation] Regulation of cell competition by engulfment receptors in Drosophila.：貪食受容体による細胞競合調節機構 (2019)
  • Author(s): 永長一茂, 野中さおり, 中井雄治, 中西義信
  • Organizer: 第92回生化学会大会
• [Presentation] Consequences of viral infection in Drosophila melanogaster (2019)
  • Author(s): 中西義信
  • Organizer: International Conference of Pharmacy Lambung Mangkura University: Therapeutic Strategy for Infectious Disease
  • Int'l Joint Research / Invited
• [Presentation] 宿主感知による細菌の遺伝子発現変動と宿主との共存 (2019)
  • Author(s): 白土明子
  • Organizer: 日本生化学会北海道支部例会 総説講演
  • Invited
• [Presentation] 変異細胞の除去をターゲットとした潜在的ながん予防食品探索 (2019)
  • Author(s): 永長一茂, 福田覚, 泉ひかり
  • Organizer: 第26回日本がん予防学会学術大会
• [Presentation] ショウジョウバエ遺伝学を用いた疾患モデル研究の展開 (2019)
  • Author(s): 白土明子
  • Organizer: 札幌医科大学病態生理リサーチカンファレンス
  • Invited