Analysis of endothelial cells presenting antigens to helper T cells in tumor microenvironment

• Project/Area Number: 18K07299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kochi University
• Principal Investigator: Shimizu Takeyuki 高知大学, 教育研究部医療学系基礎医学部門, 准教授 (10339137)
• Co-Investigator(Kenkyū-buntansha): 宇高 恵子 高知大学, 教育研究部医療学系基礎医学部門, 教授 (40263066) ; 小松 利広 高知大学, 教育研究部医療学系基礎医学部門, 助教 (90598517)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん免疫 / T細胞 / 抗原提示 / 血管内皮細胞 / miRNA / 遺伝子 / ヘルパーT細胞 / 腫瘍免疫

Outline of Final Research Achievements

In the tumor microenvironment, endothelial cells (ECs) can present tumor antigens to helper T cells. Gene expressions were compared in cultured ECs after stimulation to induce antigen presentation. miRNAs which were differentially expressed after stimulation were identified. The expressions of these miRNAs were analyzed in mouse tumor model. Some miRNAs were differentially expressed between ECs from tumor and normal tissues. The quantities of miRNAs in plasma samples of cancer patients were also analyzed. These miRNAs may be candidates for markers of immunoreactions against tumors.

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は、近年注目されている治療法であり、その効果や有効性を測定する指標が必要である。本研究は、免疫反応の進行する場に特徴として、ヘルパーT細胞に抗原提示をする腫瘍組織内血管内皮細胞の存在に注目した。そして、このような血管内皮細胞の遺伝子発現の特徴を明らかにし、それを指標として腫瘍に対する免疫反応を検出することを試みた。今後の研究の発展によって、新たな視点からがん免疫反応をモニターできる可能性がある。

Research Products

• [Journal Article] Carboxylated polyamidoamine dendron-bearing lipid-based assemblies for precise control of intracellular fate of cargo and induction of antigen-specific immune responses. (2020)
  • Author(s): Eiji Yuba , Yoshikatsu Sugahara, Yuta Yoshizaki, Takeyuki Shimizu, Michiyuki Kasai, Keiko Udaka, Kenji Kono
  • Journal Title: Biomater Sci Volume: 9 Issue: 8 Pages: 3076-3089
  • DOI: 10.1039/d0bm01813a
  • NAID: 120007026014
  • Peer Reviewed
• [Journal Article] Development of a novel monoclonal antibody that binds to most HLA-A allomorphs in a conformation-dependent yet peptide-promiscuous fashion (2020)
  • Author(s): Toshihiro Komatsu, Takeyuki Shimizu, Makoto Kanoh, Tomoya Miyakawa, Yoko Satta, Yoshiki Yasukochi, Rika Fujimoto, Motoki Tada, Kaori Machida, Sayo Kataoka, Keiko Udaka
  • Journal Title: Immunogenetics Volume: 72 Issue: 3 Pages: 143-153
  • DOI: 10.1007/s00251-020-01154-w
  • Peer Reviewed
• [Journal Article] High-affinity IgM+ memory B cells are defective in differentiation into IgM antibody-secreting cells by re-stimulation with a T cell-dependent antigen (2018)
  • Author(s): Yasuyuki Tashiro, Akikazu Murakami, Yasuyoshi Hara, Takeyuki Shimizu, Masato Kubo, Ryo Goitsuka, Hidehiro Kishimoto, Takachika Azuma
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 14559-14559
  • DOI: 10.1038/s41598-018-32926-w
  • Peer Reviewed / Open Access
• [Presentation] Optimization of culture condition and method of detection to monitor T cells specific for HLA-peptides in PBMCs (2021)
  • Author(s): Keiko Udaka, Asami Nakata, Kaori Machida, Toshihiko Komatsu, Takeyuki Shimizu
  • Organizer: 第24回日本がん免疫学会総会
• [Presentation] Construction of a platform to predict HLA-A*11:01-binding peptides (2019)
  • Author(s): 小松利広、清水健之、町田香織、山下慶子、中村祥紀、宇高恵子
  • Organizer: 第23回日本がん免疫学会総会
• [Presentation] ゲノム編集によるTAP欠損細胞を使ったMHCクラスI分子と抗原ペプチドの結合相互作用解析法 (2019)
  • Author(s): 清水健之、小松利広、深澤太郎、片岡佐誉、宇高恵子
  • Organizer: 第23回日本がん免疫学会総会
• [Presentation] Construction of a computational platform to predict HLA-A*11:01 binding peptides (2019)
  • Author(s): Keiko Udaka, Toshihiro Komatsu, Takeyuki Shimizu
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Development of a novel monoclonal antibody which binds to most HLA-A allomorphs in a peptide-dependent, yet sequence promiscuous fashion (2018)
  • Author(s): Makoto Kanoh, Takeyuki Shimizu, Toshihiro Komatsu, Yuko Satta, Sayo Kataoka, Keiko Udaka
  • Organizer: 第47回日本免疫学会学術集会