|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Growth of tumor cells is caused by unbalance of immune responces. In patients with tumor, cellular immunoresponce of peripheral blood is declined compared with healthy controls, and this low-immunoresponse is thought to cause tumor growth. Recently, we reported that cytokines (TNF-alpha, GM-CSF,IL-6 et.a1 ) were related with the generation, metastasis and invasion of liver tumor, especially TNF-alpha rised according to progress of tumor. In this study, (we investigated whether cytokines and cellular adhesion molecules (ICAM-1) interacted with tumor metastasis and invasion, and low immunoresponse of patitnts with liver tumor.
1) Serum levels of TNF-alpha, GM-CSF,IL-1,2,6 were high in patients with liver tumor. The levels of TNF-alpha, GM-CSF and ICAM-1 in tumor tissue, IL-1,2,6 and
ICAM-1 in non-tumor tissue were also high. ICAM-1 was detected in supernatant of established tumor cell line (MS-1), and surprisingly the production of ICAM-1 was increased by stimulation with TNF-alpha, GM-CSF
,IFN-gamma or IL-1. Moreover, ICAM-1 (CD54) levels on cell surface of MS-1 was also increased by the stimulation with these cytokines. These increase were verified by immuno-staining in liver tumor tissue.
Growth of tumor cells were related with the Ievels of cell surface B7-1 and B7-2, so we investigated the change of these cell surface markers in MS-1 by treatment with cytokines.
B7-1 level of MS-1 was increased by treatment of TNF-alpha and GM-CSF,and these increase were related with the concentration of cytokines. Though, on the contrary, B7-2 was decreased by these treatment.
2) Tne function of peripheral and tumor-infilated lymphocyte (PBL and TIL,respectively) were declined in patients with tumor compared with healthy controls. But, the response of TPA was increased in patients.
MS-1 was cultured more than two years without transformation, and fortunately, auto-lymphocytes were able to obtain by patient orginated of this cell line. So, we compared killar activity to MS-1 between auto- and allo lymphocytes.
Anto-lymphocytes had 34% of killar activity, and this activity was increased by the treatment of TNF-alpha, IFN-gamma and IL-6.
From these results, TNF-alpha, GM-CSF,IL-6 et.a1.induced co-stimulatory factor on tumor cell surface, and these induction was related to the activation of CTL in patients with liver tumor. Less