Elucidation of T cell infiltration mechanism into the tumor tissue by the antigen recognition

• Project/Area Number: 16K14611
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kochi University
• Principal Investigator: Komatsu Toshihiro 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): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血管内皮細胞 / 抗原提示 / 腫瘍抗原 / 細胞傷害性T細胞 / MHC class I 分子 / T細胞 / 腫瘍 / 免疫学 / 腫瘍細胞

Outline of Final Research Achievements

In this study, we found that cross-presentation of tumor antigen by tumor endothelial cells(tECs) promotes infiltration of tumor specific CTLs in tumors. We developed in vivo method to evaluate the infiltration of tumor specific CTLs in tumors by recognition of tumor antigen on tECs. We found that material “X” which promotes cross-presentation by tEC induced strong tumor regression.

Research Products

• [Journal Article] Knockout of the interleukin-36 receptor protects against renal ischemia-reperfusion injury by reduction of proinflammatory cytokines (2018)
  • Author(s): Nishikawa H, Taniguchi Y, Matsumoto T, Arima N, Masaki M, Shimamura Y, Inoue K, Horino T, Fujimoto S, Ohko K, Komatsu T, Udaka K, Sano S, Terada Y.
  • Journal Title: Kidney Int. Volume: 93 Issue: 3 Pages: 599-614
  • DOI: 10.1016/j.kint.2017.09.017
  • Peer Reviewed / Open Access
• [Journal Article] Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes. (2016)
  • Author(s): Yoshizaki Y, Yuba E, Komatsu T, Udaka K, Harada A, Kono K
  • Journal Title: Molecules Volume: 21 Issue: 10 Pages: 1284-1284
  • DOI: 10.3390/molecules21101284
  • Peer Reviewed / Open Access
• [Presentation] 固形腫瘍内へのT細胞の浸潤機構 (2018)
  • Author(s): 小松 利広
  • Organizer: 新学術領域研究「ネオ・セルフの生成・機能・構造」 第1回 若手の会（第2回 領域班会議）
• [Presentation] Extravasation of CTLs occurs by recognizing the MHC-peptide complexes cross-presented by vascular endothelial cells (2017)
  • Author(s): Toshihiro Komatsu, Ryosuke Iwade, Mika Kijima, Takehito Sato, Keiko Udaka
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] Construction of a TAP deficient HLA class I-binding assay system with the use of CRISPR/Cas9 system (2017)
  • Author(s): Takeyuki Shimizu, Toshihiro Komatsu, Keiko Udaka
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] Cross-presentation of tumor antigen by endothelial cells promotes infiltration of tumor specific CTLs (2016)
  • Author(s): Komatsu T, Iwade R, Sato T, Udaka K
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] 血管内皮細胞のHLAクラスII発現は、T細胞浸潤及び膵腫瘍に対する傷害活性と関連する (2016)
  • Author(s): 宇高 恵子、木岐 淳、西森 功、西原 利治、小松 利広、西岡 千恵、鈴木 勝英
  • Organizer: 第8回血液疾患免疫療法学会学術集会
  • Place of Presentation: 北海道大学(北海道札幌市)
  • Year and Date: 2016-09-03
• [Presentation] 血管内皮細胞のクロスプレゼンテーションによるCTLの固形腫瘍への抗原特異的浸潤 (2016)
  • Author(s): 岩出 良介、横山 水紀、小松 利広、木嶋 美香、笠井 道之、清水 健之、佐藤 健人、宇高 恵子
  • Organizer: 第15回四国免疫フォーラム
  • Place of Presentation: 高知大学（高知県南国市）
  • Year and Date: 2016-06-25