| Project/Area Number |
05670444
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KOYAMA Shohei University of Tsukuba Dept.of Internal Medicine, Assistant Professor., 臨床医学系, 講師 (00110502)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAO Katashi Univ.of Tsukuba, Department of Surgery, Professor., 臨床医学系, 教授 (50091921)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | gastric carcinoma / anti-tumor immunity / suppressor cells / adhesion molecule / ICAM-1 / LFA-1 / killer cells / Escape mechanisms of the tumor. |
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| Research Abstract |
1) The present study clearly demonstrates the existence of suppressor cells in freshly prepared PBL of patients with primary advanced gastric carcinoma that suppress the effector process of tumor cytolytic activity of lymphokine activated killer (LAK) cells. The suppressive effect was mediated mainly by the nylon-wool adherent cells.but not by nylon-wool passed cells. The suppressor-effector cells from nylon-wool adherent cells could be regarded as lymphocytes with two distinct surface type by the method of negative or positive selection studies : CD8^+T and CD8^-CD11b^+ cells. However, the CD4^+T cells in nylon-wool adherent cells did not suppress the effector phase of tumor killing.
2) To operate the suppressor cell activity, cell-cell contact (effector-target cells) via the pathways of LFA-1/ICAM-1, CD2/LFA-3, TCR/CD3 complex or CD8 is prerequisite at least.
3) Administration of anticancer drugs, such as Mitomicin C and Tegafur, or CDDP and Tegafur to patients with gastric carcinoma reduced the suppressor cell activity.
4) ICAM-1 antigen expressed on the tumor cells was also observed as shedding ICAM-1 antigen in circulating blood or ascites or cultured supernatant. Our study demonstrates that shedding ICAM-1 antigen can bind to LFA-1 antigen on activated LAK cells, resulting in lower cell-mediated cytotoxicity. This phenomena may have profound implications for down-regulation of the immune system and for enhancing the tumor metastatic capacity in cancer patients.
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