Jachimczak P, Schwulera U, Bogdahn U
Department of Neurology, University of Würzburg, Germany.
J Neurosurg. 1994 Oct;81(4):579-86. doi: 10.3171/jns.1994.81.4.0579.
The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-beta) for PBMC's. Lymphokine-activated PBMC's secrete IL-1 alpha, IL-2, IL-4, IL-6, interferon-gamma, and tumor necrosis factor-alpha, which may modulate glioma cell proliferation. None of these cytokines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance glioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.
采用标准的和改良的（用可渗透膜分隔）混合淋巴细胞肿瘤细胞（MLTC）培养方法，研究了三种恶性胶质瘤早期传代细胞培养物与体外白细胞介素（IL）-1α和IL-2激活的自体外周血单个核细胞（PBMC）之间的体液相互作用。在改良的MLTC中，胶质瘤细胞明显抑制PBMC的增殖（高达60%），而淋巴因子激活的PBMC可使胶质瘤细胞生长增强高达12倍，这是通过3H-胸腺嘧啶掺入试验确定的。胶质瘤细胞产生对PBMC有刺激作用的蛋白（IL-6）和抑制作用的蛋白（转化生长因子-β）。淋巴因子激活的PBMC分泌IL-1α、IL-2、IL-4、IL-6、干扰素-γ和肿瘤坏死因子-α，这些因子可能调节胶质瘤细胞的增殖。这些细胞因子中没有一种能像改良的MLTC系统那样强烈地刺激胶质瘤细胞。这些观察结果表明，体外淋巴因子激活的PBMC虽然受到胶质瘤来源的体液因子的抑制，但可能通过分泌到培养基中的可溶性因子增强胶质瘤细胞的增殖。作者得出结论，胶质瘤-淋巴细胞生长调节网络包括来自两个细胞群体的刺激和抑制因子，这些因子可能调节肿瘤进展。这些观察结果可能与胶质瘤患者的过继性免疫治疗有关。
