A novel approach to analyze the immunological responses in human colorectal carcinoma

• Project/Area Number: 13671275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: MIZOI Takayuki Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (90271949)
• Co-Investigator(Kenkyū-buntansha): ISHII Seiichi Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (60221066) ; 大谷 明夫 東北大学, 大学院・医学系研究科, 助教授 (30133987)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: colorectal carcinoma / tumorimmunology / macrophage / dendritic cell / lymphocyte / flowcytometry / 樹状細胞

Research Abstract

1: Flowcytometric analyses of macrophages, dendritic cells, and lymphocytes isolated from colorectal cancer(CRC) tissue
(1) We isolated mononuclear cells from colorectal tumors and normal colorectal tissues by enzymatic digestion and Ficoll-Paque separation.
(2) Flowcytometric analyses showed more CD14-positive macrophages in the invasive margin of CRC than in normal mucosal fissue.
(3) T cells derived from CRC were CD4-dominant compared to peripheral blood lymphocytes (PBL) and more than 90 % of those were memory T lymphocytes.
(4) The T cells isolated from CRC were Th 1-dominant compared to PBL and positive for type l chemokines, CXCR3 and CCR5.
(5) A mixed lymphocyte reaction experiment demonstrated that CD14-positive macrophages located in CRC possessed the ability to stimulate T cell responses.
2: lmmunohistochemlcal analyses
(1) lmmunohistochemical expression of the surface antigens in mononuclear cells in tumor was consistent with the data of the flowcytometric analyses.
(2) Macrophages along the invasive margin of CRC were Fas ligand (FasL)-positive. The number of apoptotic cancer cells around the FasL-positive macrophages was correlated with the number of the FasL-positive macrophages.
(3) CD4+ T cells and CD8+ T cells were positive for CXCR3 and CCR5. CD8+ T lymphocytes expressed RANITES, and cancer cells and macrophages expressed IP- 10.

Research Products

• [Publications] Sugita J et al.: "Close association between Fas ligand-positive tumor-associated macrophages and apoptotic cancex cells along invasive margin of colorectal carcinoma aproposal on tumor-host interactions"Jpn.J.Cancer Res.. 93. 320-328 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sugita J: "Close association between Fas ligand-positve tumor-associated macrophages and apoptotic cancer cells along invaslve margin of colorectal carcinoma: a proposal on tumor-host interactions."Jpn. J. Cancer Res.. 93. 320-328 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sugita J et al.: "Close association between Fas ligand-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma : a proposal on tumor-host interactions"Jpn. J. Cancer Res.. 93. 320-328 (2002)
• [Publications] Sugita, J. et al.: "Close association between Fas 1 ligand(FasL ; CD95L)-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma : A new paradigm of tumar-host interactions"Japanese Journal of Cancer Research. (in press). (2002)