The analysis of the mechanism to induce the tumor specific immune responses by the anti-cancer agents and its clinical utilization

• Project/Area Number: 23659632
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hokkaido University
• Principal Investigator: TSUCHIKAWA Takahiro 北海道大学, 北海道大学病院, 助教 (50507572)
• Co-Investigator(Kenkyū-buntansha): HIRANO Satoshi 北海道大学, 大学院・医学研究科, 教授 (50322813) ; NAKAMURA Toru 北海道大学, 大学院・医学研究科, 助教 (70645796) ; 宮本 正樹 北海道大学, 大学病院, 助教 (40333611)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: TMA解析 / 胆道癌 / マーカー / 抗癌剤 / 免疫原性増強 / ＨＬＡ / classI発現増強 / 食道癌術前化学療法 / Immunogenic cell death

Research Abstract

We investigated the immune responses induced by neoadjuvant chemotherapy in esophageal cance and pancreatic cancer and clarified the increase of the CD4,CD8,CD45RO positive lymphocytes and the decrease of the Treg cells in the tumor microenvironment compared with the specimen without neoadjuvant chemotherapy. Next, we evaluated the optimal concentration of the anti cance agents to induce immunogenic cell death, and injected them into the lateral side of the mouse followed by the transplantation of the fresh viable cells into the contar-lateral side. The implanted tumor did not grow with lymphocytes and dendritic cells infiltrated ihn the microenvironment.At the present,we are now analyzing the subpopulation of the lymphocytes and their specificity to the tumor.

Research Products

• [Journal Article] Novel aspects of preoperative chemo(radiation)therapy improving anti-tumor immunity in pancreatic cancer. (2013)
  • Author(s): Tsuchikawa T, Hirano S, Tanaka E, Matsumoto J, Kato K, Nakamura T, Ebihara Y, Shichinohe T.
  • Journal Title: Cancer Sci Volume: 104(5) Pages: 531-5
  • Peer Reviewed
• [Journal Article] Surgical strategy for liver metastases of neuroendocrinetumors (2012)
  • Author(s): Tsuchikawa T, Hirano S, Tanaka E, Kato K, Matsumoto J, Nakayama T, Tabata Y, Shichinohe T
  • Journal Title: Hepato-Gastroenterol Volume: 59(115) Pages: 921-3
  • Peer Reviewed
• [Journal Article] Multidisciplinary treatment strategy for advanced pancreatic neuroendocrine tumors A single center experience. (2012)
  • Author(s): Tsuchikawa T, Hirano S, Tanaka E, Kato K, Matsumoto J, Sichinohe T.
  • Journal Title: Hepato-Gastroenterol.Nov-Dec Volume: 59(120) Pages: 2623-6
  • Peer Reviewed
• [Journal Article] The immunological impact of neo-adjuvant chemotherapy on tumor microenvironment of the esophageal squamous cell carcinoma. (2012)
  • Author(s): Tsuchikawa T, Miyamoto M, Yamamura Y, Shichinohe T, Hirano S, Kondo S.
  • Journal Title: Ann Surg Oncol Pages: 1713-9
  • Peer Reviewed
• [Journal Article] Extensively spreading intraepithelial bile duct carcinoma causing multiple bile duct strictures (2011)
  • Author(s): Tsuchikawa T, Kondo S, Hirano S, Tanaka E, Kato K, Matsumoto J, Kubota K, Shichinohe T.
  • Journal Title: Report of 3 cases. Surg Today Volume: 41 Pages: 1674-1679
  • Peer Reviewed
• [Journal Article] Association of CD8+ T cell infiltration in esophageal carcinoma lesions with human leucocyte antigen (HLA) class I antigen expression and survival (2011)
  • Author(s): TsuchikawaT, Ikeda H, Cho Y, Miyamoto M, Shichinohe T, Hirano S, Kondo S.
  • Journal Title: Clin Exp Immunol Volume: 164 Pages: 50-56
  • Peer Reviewed
• [Journal Article] Distal pancreatectomy and portal vein resection without vascular reconstruction for endocrine tumors with massive intraportal growth. (2011)
  • Author(s): Tsuchikawa T, Kondo S, Hirano S, Tanaka E, Kawasaki R, Kato K, Matsumoto J, Shichinohe T
  • Journal Title: Hepato-Gastroenterol Volume: 58 Pages: 1029-1031
  • Peer Reviewed
• [Presentation] 消化器腫瘍術後にDICを合併した症例 に対するリコモジュンTMの使用経験 (2012)
  • Author(s): 土川貴裕
  • Organizer: 第2012北海道敗血症フォーラム
  • Place of Presentation: 札幌グランドホテル別館(札幌市)
  • Year and Date: 2012-08-25
• [Presentation] あきらめない。チームで支える膵がん外科治療演者 (2012)
  • Author(s): 土川貴裕
  • Organizer: 第3回北大病院腫瘍センター・市民公開講座
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2012-06-09
• [Presentation] 局所進行膵体部癌の集学的治療における局所制御術式DP-CARの意義 (2012)
  • Author(s): 土川貴裕,平野聡,田中栄一
  • Organizer: 第20日本消化器関連学会週間(JDDW)
  • Place of Presentation: 神戸国際展示場、ポートピアホテル、神戸国際会議場(神戸市)
• [Presentation] DP-CARによる局所制御と集学的治療 による進行膵体部癌の治療戦略 (2012)
  • Author(s): 土川貴裕,平野聡,野路武寛,加藤健太郎,松本譲,七戸俊明,田中栄一
  • Organizer: 第67回日本消化器外科学会総会
  • Place of Presentation: 富山国際会議場(富山市
• [Presentation] Modified DPPHR(Duodenum-Preserving Resection of the Head of the Pancreas) for the low grade malignant lesion in the pancreas head (2012)
  • Author(s): Tsuchikawa T
  • Organizer: 第10回World Congress of the International Hepato-Pancreato-Biliary Association (IHPBA)
  • Place of Presentation: PALAIS DES CONGRES (Paris,France)
• [Presentation] Modified DPPHR(Duodenum-Preserving Resection of the Head of the Pancreas) for the benign or low grade malignant lesion in the pancreas head (2012)
  • Author(s): Tsuchikawa T, Hirano S, Tanaka E, Matsumoto J, Kato K, Noji T, Shichinohe T
  • Organizer: 第24回日本肝胆膵外科学会
  • Place of Presentation: 大阪国際会議場(大阪市)
• [Presentation] 食道癌術前化学療法が癌局所環境に及ぼす免疫学的変化に関する検討 (2011)
  • Author(s): 土川貴裕,宮本正樹,山村喜之,京極 典憲,黒田 晶,真木健裕,田中栄一,七戸 俊明,平野 聡
  • Organizer: 第9回日本消化器外科学会大会
  • Place of Presentation: 福岡国際センター、福岡サンパレス、福岡国際会議場、マリンメッセ福岡(福岡市) 演題名
• [Presentation] 胆管癌垂直進展範囲におけるMDCT-MPR像と病理像との対比 (2011)
  • Author(s): 土川貴裕,平野 聡,田中栄一
  • Organizer: 第47回日本胆道学会
  • Place of Presentation: ワールドコンベンションセンターサミ ット(宮崎市)
• [Presentation] Treatment strategy for livermetastases of pancreatic neuroendocrine tumors (2011)
  • Author(s): Tsuchikawa T, Hirano S, Tanaka E, Kato K, Matsumoto J, Nakayama T, Tabata Y, Shichinohe T
  • Organizer: 第4回AOPA&KPBA
  • Place of Presentation: Lotte Hotel Jeju(Korea)
• [Presentation] 科における難治性胆汁瘻予防のための工夫と対策 (2011)
  • Author(s): 土川貴裕,平野聡,田中栄一,加藤 健太郎,松本譲,七戸俊明,近藤哲
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] 膵頭十二指腸切除術後の膵液瘻?重症化の予測因子とその対策? (2011)
  • Author(s): 土川貴裕,平野聡,田中栄一,加藤 健太郎,松本譲,高田実,田本英司,寺本賢一,村上壮一,川村武史,中山智英,三浦巧,齋藤博紀,七戸俊明,近藤哲
  • Organizer: 第23回日本肝胆膵外科学会
  • Place of Presentation: 京王プラザホテル(東京)