Hirte H W, Clark D A
Ontario Cancer Treatment and Research Foundation-Hamilton Regional Cancer Centre, Canada.
Cell Immunol. 1991 Aug;136(1):122-32. doi: 10.1016/0008-8749(91)90387-q.
Lysis of human ovarian carcinoma cells by natural killer (NK) cells, interferon-alpha activated NK cells (alpha-NK) and lymphokine-activated killers cells (LAK) was studied using both fresh tumor cells and a cell line (HEY) as targets. A clonogenic assay to measure cell kill was more sensitive than a 4-h 51Cr release assay. Both assays showed that single cells were more effectively lysed than were tumor clumps (spheroids). Freshly isolated tumor cells studied in the 51Cr release assay appeared equally susceptible to lysis by LAK cells whether in the form of clumps or single cells, but NK and alpha-NK effectors appeared much less effective in lysing susceptible target cells when they were in clumps. Tumor cells from some patients showed marked resistance to lysis by NK and alpha-NK cells in fractions enriched for clonogenic cells, even when tested in a single cell-suspension, whereas LAK cells were always cytolytic. These data suggest that intrinsic resistance of ovarian carcinoma to lysis by LAKs is unlikely to explain failure of LAK + IL-2 therapy to eradicate tumor in vivo.
利用新鲜肿瘤细胞和一种细胞系（HEY）作为靶标，研究了自然杀伤（NK）细胞、α-干扰素激活的NK细胞（α-NK）和淋巴因子激活的杀伤细胞（LAK）对人卵巢癌细胞的杀伤作用。一种用于测量细胞杀伤的克隆形成试验比4小时的51Cr释放试验更敏感。两种试验均表明，单细胞比肿瘤团块（球体）更容易被有效杀伤。在51Cr释放试验中研究的新鲜分离肿瘤细胞，无论以团块还是单细胞形式存在，似乎对LAK细胞的杀伤同样敏感，但NK和α-NK效应细胞在杀伤成团的敏感靶细胞时效果要差得多。来自一些患者的肿瘤细胞在富含克隆形成细胞的组分中对NK和α-NK细胞的杀伤表现出明显抗性，即使在单细胞悬液中进行检测时也是如此，而LAK细胞始终具有细胞毒性。这些数据表明，卵巢癌对LAK杀伤的内在抗性不太可能解释LAK + IL-2疗法在体内根除肿瘤失败的原因。
