|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1992 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1991 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1990 : ¥1,500,000 (Direct Cost : ¥1,500,000)
This study was designed to investigate whether lymph node cells could exert an antiproliferative activity on tumor cells that are mediated through cytokines. The soluble antitumor activity of regional lymph node cells obtained from patients with cervical cancer was investigated by using a human tumor clonogenic assay (HTCA). A significant antiproliferative activity of the lymph node cells (LNCs) against a cervical cancer cell line, HeLa cells, was demonstrated by stimulation with either phytohemagglutinin (PHA) or concanavalin A(ConA), but not with interleukin-2(IL-2). In addition, a significant antiproliferative activity of the LNCs obtained from cervical cancer and endometrial cancer patients against a endometrial cancer cell line, RL95-2, was also demonstrated when they were stimulated by PHA. This antiproliferative activity was found mainly in nonadherent cells, possibly T-cells. LNCs produced both interferon gamma(IFNgamma) and tumor necrosis factor (TNF), and it was demonstrated that HeLa cells were sensitive to recombinant human IFNgamma and RL95-2 cells were sensitive to recombinant human TNF. These findings suggested the antitumor activities were attributed to IFNgamma and TNF, respectively. Moreover, about HeLa cells, it was confirmed that IFNgamma was responsible for the activity by using neutralizing experiments. These results indicate that human LNCs were able to exert an antiproliferative activity mediated through the cytokines by appropriate stimulation. In the two studies, LNCs could not demonstrate an antiproliferative activity by stimulation with IL-2, but peripheral blood lymphocytes, in some cases, exerted antiproliferative activity by stimulation with IL-2 on HTCA (submitted paper). In addition, LNCs produced cytokines, such as TNFalpha, TNFbeta, and IFNgamma when they were stimulated by IL-2 for longer duration (ongoing study). IL-2 stimulation on LNCs might be a promising procedure, so it is presently under intensive research investigation.