Characterization and induction of antitumor lymphokine derived from human lymph node cell

人淋巴结细胞来源的抗肿瘤淋巴因子的表征和诱导

基本信息

批准号：
02670746
负责人：
SAITO Toshiaki
金额：
$ 1.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670746/
关键词：
lymph node lymphocyte lymphokine interferon tumor necrosis factor antitumor activity インタ-フェロン TNF 抗腫瘍療法

项目摘要

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.

这项研究旨在研究淋巴结细胞是否可以在通过细胞因子介导的肿瘤细胞上发挥抗增殖活性。使用人类肿瘤克隆性测定（HTCA）研究了从宫颈癌患者获得的区域淋巴结细胞的可溶性抗肿瘤活性。淋巴结细胞（LNC）对宫颈癌细胞系HELA细胞的显着抗增殖活性，通过用植物性甲状腺凝集素（PHA）或contanavalin a（CONA）刺激证明，但没有使用Interleukin-2（ILIL-2）。此外，还证明了从宫颈癌和子宫内膜癌患者获得子宫内膜癌细胞系RL95-2的LNC的显着抗增生活性，当它们被PHA刺激时。这种抗增生活性主要在非粘附细胞中，可能是T细胞。 LNC既产生了干扰素伽马（IFNGAMMA）和肿瘤坏死因子（TNF），并且证明HeLa细胞对重组人IFNGAMMA和RL95-2细胞对重组对重组人类TNF敏感。这些发现表明，抗肿瘤活性分别归因于Ifngamma和TNF。此外，关于HeLa细胞，可以通过使用中和实验来确认IFNGAMMA负责该活动。这些结果表明，人LNC能够通过适当的刺激通过细胞因子介导的抗增殖活性。在这两项研究中，LNC无法通过IL-2刺激IL-2刺激抗增殖活性，但是在某些情况下，通过对HTCA上的IL-2刺激施加了抗增殖活性（提交的论文）。此外，当LNC在更长的持续时间内刺激IL-2时，LNC会产生细胞因子，例如tnfalpha，tnfbeta和ifngamma（正在进行的研究）。 IL-2对LNC的刺激可能是一个有前途的程序，因此目前正在进行密集的研究研究中。