Peritoneal dissemination of gastric cancer stem cells and immunotherapy overcoming immune escape

• Project/Area Number: 23591939
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: 独立行政法人国立国際医療研究センター (2012-2013); Kyushu University (2011)
• Principal Investigator: TSUJITANI Shunichi 独立行政法人国立国際医療研究センター, その他部局等, その他 (30188544)
• Co-Investigator(Kenkyū-buntansha): KEKEJI Yoshihiro 神戸大学, 大学院食道胃腸外科, 教授 (80284488) ; MORIT Masaru 国立病院機構九州がんセンター, 消化器外科, 部長 (30294937) ; KOHNOE Shunji 田川市立病院, 院長 (30215199) ; EGASHIR Akinori 国立病院機構九州がんセンター, 消化器外科 (00419524) ; SONODA Hideto 伊万里有田共立病院, 外科, 医長 (00465725) ; OHGA Takefumi 国立病院機構福岡東医療センター, 外科, 部長 (60335958)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん幹細胞 / 免疫回避機構 / 樹状細胞 / 免疫抑制 / 胃癌 / 腹膜播種

Research Abstract

Peritoneal dissemination of gastric cancer stem cells and immunotherapy overcoming immune escape were investigated. Cultured gastric cancer cell lines MKN45 and MKN74 were sorted by FACS int0 CD44+ and CD44- cells. CD44+ gastric cancer cells expressed TGF-b , IL-10 and VEGF. Therefore, gastric cancer stem cells may have high potential to escape from immune surveillance. However, CTL from healthy donor co-cultured with CD44+ gastric cancer cells could kill CD44+ gastric cancer cells as well as that CTL co-cultured with CD44- gastric cancer cells could kill CD44- gastric cancer cells. These results indicate that cancer stem cells may not be resistant to immunotherapy but the cancer stem cells may be protected by strong escape mechanisms provided by host cells.

Research Products

• [Journal Article] Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer : a randomized controlled trial (2014)
  • Author(s): Tatebe S, Tsujitani S, Nakamura S, Shimizu T, Yamane N, Nishidoi H, Kurisu Y,Kanayama H, Ogawa H, Ikeguchi M.
  • Journal Title: Gastric Cancer Volume: 17(3) Pages: 508-13
  • NAID: 40020216078
• [Journal Article] Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer (2014)
  • Author(s): Hirabayashi S, Kosugi S, Isobe Y, Nashimoto A, Oda I, Hayashi K, Miyashiro I,Tsujitani S, Kodera Y, Seto Y, Furukawa H, Ono H, Tanabe S, Kaminishi M, Nunobe S, Fukagawa T, Matsuo R, Nagai T, Katai H, Wakai T, Akazawa K.
  • Journal Title: Ann Oncol Volume: 25(6) Pages: 1179-84
  • DOI: 10.1093/annonc/mdu125
• [Journal Article] Impact of dendritic cell vaccines pulsed with Wilms' tumor-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers. (2013)
  • Author(s): Hidenori Takahashi
  • Journal Title: Eur J Cancer. Volume: 49 Pages: 852-859
  • DOI: 10.1016/j.ejca.2012.11.005
  • Peer Reviewed
• [Journal Article] Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer. (2013)
  • Author(s): Kobayashi M, Sakabe T, Abe H, Tanii M, Takahashi H, Chiba A, Yanagida E,Shibamoto Y, Ogasawara M, Tsujitani S, Koido S, Nagai K, Shimodaira S, Okamoto M,Yonemitsu Y, Suzuki N, Nagaya M; DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT).
  • Journal Title: J Gastrointest Surg Volume: 17(9) Pages: 1609-1617
  • Peer Reviewed
• [Journal Article] Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry (2013)
  • Author(s): Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, Tsujitani S, Seto Y, Furukawa H, Oda I, Ono H, Tanabe S, Kaminishi M
  • Journal Title: Gastric Cancer Volume: 16 Pages: 1-27
  • Peer Reviewed
• [Journal Article] Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. (2012)
  • Author(s): Tsujitani S, Saito H, Wakatsuki T, Ikeguchi M, Shirabe K, Morita M, Kakeji Y,Yano T, Maehara Y.
  • Journal Title: Surg Today Volume: 42(3) Pages: 225-232
  • NAID: 10030231066
  • Peer Reviewed
• [Journal Article] Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN(®)): review of development and future perspectives. (2012)
  • Author(s): Maehara Y, Tsujitani S, Saeki H, Oki E, Yoshinaga K, Emi Y, Morita M, Kohnoe S, Kakeji Y, Yano T, Baba H
  • Journal Title: Surgery Today Volume: 42 Pages: 8-28
  • Peer Reviewed
• [Journal Article] Role of tumor-associated macrophages in the progression of hepatocellular carcinoma (2012)
  • Author(s): Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T, Takeishi K, Uchiyama H, Yoshizumi T, Taketomi A, Morita M, Tsujitani S, Sakaguchi Y, Maehara Y.
  • Journal Title: Surg Today Volume: 42(1) Pages: 1-7
  • NAID: 10030230041
• [Journal Article] Prognostic effects of oral anti-cancer drugs as adjuvant chemotherapy for 2 years after gastric cancer surgery (2012)
  • Author(s): Okuyama T, Korenaga D, Edagawa A, Itoh S, Oki E, Kawanaka H, Ikeda Y, Kakeji Y, Tateishi M, Tsujitani S, Takenaka K, Maehara Y.
  • Journal Title: Surg Today Volume: 42(8) Pages: 734-40
  • NAID: 10030948984
• [Journal Article] Prognostic effects of oral anti-cancer drugs as adjuvant chemotherapy for 2 years after gastric cancer surgery. (2012)
  • Author(s): Okuyama T, Korenaga D, Edagawa A, Itoh S, Oki E, Kawanaka H, Ikeda Y, Kakeji Y, Tateishi M, Tsujitani S, Takenaka K, Maehara Y
  • Journal Title: Surg Today. Volume: 42 Pages: 734-40
  • NAID: 10030948984
  • Peer Reviewed
• [Journal Article] Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. (2012)
  • Author(s): Tsujitani S, Saito H, Wakatsuki T, Ikeguchi M, Shirabe K, Morita M, Kakeji Y, Yano T, Maehara Y
  • Journal Title: Surg Today Volume: 42 Pages: 225-32
  • NAID: 10030231066
  • Peer Reviewed
• [Journal Article] Biological mechanism and clinical effect of protein-bound polysaccharide K(KRESTINR) : review of development and future perpectives. (2012)
  • Author(s): Maehara Y, Tsujitani S, Saeki H, Oki E, Yoshinaga K, Emi Y, Morita M, Kohnoe S, Kakeji Y, Yano T, Baba H
  • Journal Title: Surg Today Volume: 42 Pages: 8-28
  • Peer Reviewed
• [Journal Article] Role of tumor-associated macrophages in the progression of hepatocellular carcinoma (2012)
  • Author(s): Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T, Takeishi K, Uchiyama H, Yoshizumi T, Taketomi A, Morita M, Tsujitani S, Sakaguchi Y, Maehara Y
  • Journal Title: Surg Today Volume: 42 Pages: 1-7
  • NAID: 10030230041
  • Peer Reviewed
• [Presentation] Immunohistochemical detection of human telomerase reverse transcriptase in human cholangiocarcinoma and risk condiction (2013)
  • Author(s): Endo K, Tsujitani S, Yoshimoto M, Watanabe J, Tokuyasu N, Sakamoto T, Naka T, Hirooka Y, Ikeguchi M.
  • Organizer: American Association for Cancer Reserch Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer (2013)
  • Author(s): Kobayashi M, Sakabe T, Tanii M, Abe H, Takahashi H, Tsujitani S, Shimodaira S, Yonemitsu Y, Okamoto M, Nagaya M.
  • Organizer: American Association for Cancer Reserch Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Immunohistochemical detection of human telomerase reverse transcriptase in human cholangiocarcinoma and risk condition (2013)
  • Author(s): Endo K, Tsujitani S, Yoshimoto M, Watanabe J, Tokuyasu N, Sakamoto T, Naka T, Hirooka Y, Ikeguchi M
  • Organizer: American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington DC
• [Presentation] Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer (2013)
  • Author(s): Kobayashi M, Sakabe T, Tanii M, Abe H, Takahashi H, Tsujitani S, Shimodaira S, Yonemitsu Y, Okamoto M, Nagaya M
  • Organizer: American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington DC
• [Presentation] Clinical evaluation of dendritic cell based vaccines pulsed with WT1 and /or MUC1 for patients with advanced or recurrent cancers (2012)
  • Author(s): Tsujitani S, Tnii M, Yonemitsu Y, Maehara M.
  • Organizer: ESMO2012
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2012-10-12
• [Presentation] Clinical evaluation of dendritic cell based vaccines pulsed with WT1 and/or MUC1 for patients with advanced or recurrent cancers
  • Author(s): Shunichi Tsujitani, Mitsugu Tanii, Yoshikazu Yonemitsu, Yoshihiko Maehara
  • Organizer: ESMO 2012
  • Place of Presentation: Vienna, Austria