Koyama S, Fukao K
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
J Cancer Res Clin Oncol. 1994;120(4):240-7. doi: 10.1007/BF01372563.
The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b-, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8-CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wool-adherent cells. CD8+ T and possibly CD8-CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host immune surveillance system.
癌症患者细胞毒性免疫反应下调的原因尚未得到充分评估。我们之前证明，来自广泛转移的胃癌患者、具有CD8+ CD11b-表面表型的T细胞生长因子激活的外周血淋巴细胞（PBL）抑制了淋巴因子激活的杀伤细胞（LAK）介导的细胞溶解效应过程。在本研究中，我们检测了18例晚期胃癌患者和10名正常健康个体新鲜制备的PBL中的抑制细胞活性。通过记录PBL是否直接抑制LAK细胞细胞毒性的效应过程来检测抑制细胞活性。大多数癌症患者的PBL悬液显示，它们含有一群能够直接抑制细胞毒性细胞对肿瘤细胞裂解效应阶段的细胞。为了进一步分析负责抑制作用的PBL，将细胞通过尼龙毛柱。尼龙毛贴壁细胞显著增强了抑制作用，而通过柱子的细胞则消除了抑制作用。10名正常健康对照的大多数尼龙毛贴壁细胞并未抑制细胞毒性反应。为了进一步确定尼龙毛贴壁细胞中的抑制效应细胞群体，进行了使用CD8-、CD4-或CD11b包被磁珠的阴性选择研究，以及使用CD8-或CD4包被磁珠的阳性选择研究。最终结果表明，抑制效应细胞至少包括两种不同的表面表型：CD8+ T细胞和CD8-CD11b+细胞。在尼龙毛贴壁细胞中排除了CD4+ T细胞和HLA-DR+ LeuM3+巨噬细胞作为抑制细胞的可能作用。CD8+ T细胞以及可能的CD8-CD11b+细胞明显抑制了抗肿瘤免疫的传出支。这些细胞介导的选择性免疫抑制可能部分与胃癌逃避宿主免疫监视系统的机制有关。
