Sacks P G, Taylor D L, Racz T, Vasey T, Oke V, Schantz S P
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston.
Cancer Immunol Immunother. 1990;32(3):195-200. doi: 10.1007/BF01771457.
A multicellular tumor spheroid (MTS) model for head and neck cancers has been used to examine the immune function of fresh and 6-day interleukin-2(IL-2)-activated peripheral blood lymphocytes (PBL). MTS are individually cultured in the presence of effector cells, and the spheroids' growth is monitored by sizing them under an inverted microscope. Dose/response studies for IL-2 (0-100 U/ml) alone and for fresh unstimulated PBL (0-10(5) cells/MTS) showed no effects on MTS growth. IL-2-activated PBL (0-10(5) cells/MTS), in contrast, modulated MTS growth in a multiphasic pattern: MTS growth was unperturbed for the first 3 days and then growth inhibition occurred, followed by MTS disintegration. Histological analysis showed that intact MTS histoarchitecture correlated with unperturbed growth, and increasing cell sloughing and MTS dissolution and replacement by activated PBL correlated with growth inhibition and disintegration. Flow-cytometric sorting of lymphocyte subset populations indicated that it was the Leu19+CD3- cells that produced these growth-modulatory effects. In contrast to the initial LAK cell resistance of MTS, single-cell suspensions demonstrated significant lysis in standard 4-h chromium-release assays. Differences between single cells and MTS suggest a potential for tissue-like organization as a factor in lymphokine-activated killing.
一种用于头颈癌的多细胞肿瘤球体（MTS）模型已被用于检测新鲜的和经6天白细胞介素-2（IL-2）激活的外周血淋巴细胞（PBL）的免疫功能。MTS在效应细胞存在的情况下单独培养，并通过在倒置显微镜下测量其大小来监测球体的生长。单独对IL-2（0 - 100 U/ml）以及对新鲜未刺激的PBL（0 - 10⁵个细胞/MTS）进行的剂量/反应研究表明，它们对MTS生长没有影响。相比之下，经IL-2激活的PBL（0 - 10⁵个细胞/MTS）以多相模式调节MTS生长：MTS在前3天生长不受干扰，随后出现生长抑制，接着是MTS解体。组织学分析表明，完整的MTS组织结构与生长不受干扰相关，而细胞脱落增加、MTS溶解以及被激活的PBL替代与生长抑制和解体相关。淋巴细胞亚群的流式细胞术分选表明，是Leu19⁺CD3⁻细胞产生了这些生长调节作用。与MTS最初对淋巴因子激活的杀伤细胞（LAK）的抗性不同，单细胞悬液在标准的4小时铬释放试验中表现出显著的裂解作用。单细胞与MTS之间的差异表明，组织样结构作为淋巴因子激活杀伤作用中的一个因素具有潜在可能性。
